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OC(c1ccc(Cl)cc1)(c1cncnc1)c1ccccc1Cl | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 36.71 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 36.71 | ml/min/kg | false | null | null | null | null | rat liver microsomes (in vitro scaled) | rat | null | null | predicted from rat liver microsomal data | 32660295 | 0.94 | q4 | hepatic | 6967943ff0bb38b727ebe0e102f73cdac2c0ae2da7ffe6b7646490a16dbaeada | 639 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 6967943ff0bb38b727ebe0e102f73cdac2c0ae2da7ffe6b7646490a16dbaeada | c4e44f12ed5365a16f21a87da213414ca09fcbc4f4111f5620e27cd40ff7e0b9 | The in‑house predicted in vivo hepatic clearance of FNL from rat liver microsomes was 36.71 mL/min/kg, comparable with the observed in vivo CL. | 56 | |
C[C@H](CCC(=O)NCCS(=O)(=O)[O-])[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C | q4.hepatic_clearance.intrinsic_clearance.ml_min | 500 | ml/min | q4.hepatic_clearance.intrinsic_clearance.ml_min | hepatic_clearance | intrinsic_clearance | ml_min | null | null | null | rat | 500 | ml/min | false | null | null | null | null | dispersion model estimate from perfused rat liver data | rat | null | null | null | 1629793 | 0.94 | q4 | hepatic | 95cc29aeef42d31f235025811af447e70c483662b436adf7621ab9fe5fd6ca75 | 640 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 95cc29aeef42d31f235025811af447e70c483662b436adf7621ab9fe5fd6ca75 | 6ae82868d53e133d13993b965fc664e3f9ba15d62feb144d7c82b93b58de5e99 | Value reported by Smallwood et al.; derived from dispersion model fitting of perfused rat liver experiments. | Estimates of CLint for taurocholate were 500 ml/min according to Smallwood et al. and from 155 to 658 ml/min according to Roberts et al. | 85 |
O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 2,484 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 2,484 | ul/min/mg | false | null | null | null | null | pooled hlm | human | null | ugt | null | 19184618 | 0.98 | q4 | hepatic | f02142875fcbc0915cc6710508f35f843b99daeb95937df564419261cfb21450 | 669 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f02142875fcbc0915cc6710508f35f843b99daeb95937df564419261cfb21450 | 992c58eab476749a8bca06753943809bb311831a9692d1bb176d04fc3d865b7e | Hepatic intrinsic clearance mediated by UGT, measured in pooled human liver microsomes. | Hepatic CLint,UGT values were reported to be between 17 and 2,484 µl/min/mg for naloxone and quercetin, respectively. | 32 |
COc1c(C)c2c(c(O)c1CC=C(C)CCC(=O)O)C(=O)OC2 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 0 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 0 | ul/min/mg | false | null | null | null | null | pooled hlm | human | null | cyp | null | 19184618 | 0.95 | q4 | hepatic | b9730d597793e45b4bb02fee36844f1e0f8d805a47b83265d4c9df3e1e4aa473 | 670 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b9730d597793e45b4bb02fee36844f1e0f8d805a47b83265d4c9df3e1e4aa473 | 23ccbbe46dce698d4ca8f501be92ccb3397a7ea084748706f871f03bec7a2918 | No detectable CYP-mediated intrinsic clearance for mycophenolic acid in pooled human liver microsomes. | CLint,CYP values were zero detection for mycophenolic acid. | 32 |
O=c1c(O)c(-c2ccc(O)c(O)c2)oc2cc(O)cc(O)c12 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 0 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 0 | ul/min/mg | false | null | null | null | null | pooled hlm | human | null | cyp | null | 19184618 | 0.95 | q4 | hepatic | 6518d0439fa19f0abd2e2faeeb9de4b3f6174c84ba8a62d936538778c12cc185 | 671 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 6518d0439fa19f0abd2e2faeeb9de4b3f6174c84ba8a62d936538778c12cc185 | c2b61f204d8c2e3c82bc15bbca6f84da589b4d7f4e932cc7f0982f4614fd3c5d | No detectable CYP-mediated intrinsic clearance for quercetin in pooled human liver microsomes. | CLint,CYP values were zero detection for quercetin. | 32 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | 15.8 | ml/min/kg microsomal protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | hepatic_clearance | intrinsic_clearance | ml_min_kg_microsomal_protein | null | null | null | rat | 15.8 | ml/min/kg microsomal protein | true | 4.7 | unspecified_variation | null | null | liver microsomes (substrate depletion) | rat | deuterated (d‐nvs‐crf38) | null | null | 24616265 | 0.99 | q4 | hepatic | 4948db7b1c6f52eb1634d530e11a2b7a669145a06810992cb5f2b0f831b7b218 | 753 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4948db7b1c6f52eb1634d530e11a2b7a669145a06810992cb5f2b0f831b7b218 | cb69b7cd27b052511c7d328722f0a99c06ce3920b2d07477a337840108f6001a | Table 1 reports the intrinsic clearance of d‑NVS‑CRF38 (deuterated) measured by substrate depletion in rat liver microsomes as 15.8 ± 4.7 ml/min/kg microsomal protein. | 27 | |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | 10.7 | ml/min/kg microsomal protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | hepatic_clearance | intrinsic_clearance | ml_min_kg_microsomal_protein | null | null | null | human | 10.7 | ml/min/kg microsomal protein | true | 2.8 | unspecified_variation | null | null | liver microsomes (substrate depletion) | human | deuterated (d‐nvs‐crf38) | null | null | 24616265 | 0.99 | q4 | hepatic | e8a4bb357c926724b62660bdd2b04b9cf3a273818fed61182be3347c4ebccf6a | 754 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e8a4bb357c926724b62660bdd2b04b9cf3a273818fed61182be3347c4ebccf6a | 43aaefe39ac2c45ebc03defb479ee42bb7cdb2b70662553ce6c33dffbdbcdcbf | Table 1 reports the intrinsic clearance of d‑NVS‑CRF38 measured by substrate depletion in human liver microsomes as 10.7 ± 2.8 ml/min/kg microsomal protein. | 27 | |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | 2.5 | ml/min/kg microsomal protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | hepatic_clearance | intrinsic_clearance | ml_min_kg_microsomal_protein | null | null | null | rat | 2.5 | ml/min/kg microsomal protein | true | 0.4 | unspecified_variation | null | null | liver microsomes (metabolite formation) | rat | deuterated (d‐nvs‐crf38) | null | null | 24616265 | 0.99 | q4 | hepatic | b42b3c65a74968e72767f9c45a02820fda1378a38ef5ff139dd3bef1ceef0c68 | 755 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b42b3c65a74968e72767f9c45a02820fda1378a38ef5ff139dd3bef1ceef0c68 | 30c4c59567957b336c241a111817bec97a56b1c0996e61e3711247b2673a99f9 | Table 1 reports the intrinsic clearance of d‑NVS‑CRF38 measured by metabolite formation in rat liver microsomes as 2.5 ± 0.4 ml/min/kg microsomal protein. | 27 | |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | 0.85 | ml/min/kg microsomal protein | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_microsomal_protein | hepatic_clearance | intrinsic_clearance | ml_min_kg_microsomal_protein | null | null | null | human | 0.85 | ml/min/kg microsomal protein | true | 0.34 | unspecified_variation | null | null | liver microsomes (metabolite formation) | human | deuterated (d‐nvs‐crf38) | null | null | 24616265 | 0.99 | q4 | hepatic | 2d36b19a42b13abacc72b8f40054bfa55635d34c28374fa6dd5612ab55bac9f5 | 756 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 2d36b19a42b13abacc72b8f40054bfa55635d34c28374fa6dd5612ab55bac9f5 | 41071de441978ba904f032cac19d48b274a3377d9291c9e78ada7f75f3384457 | Table 1 reports the intrinsic clearance of d‑NVS‑CRF38 measured by metabolite formation in human liver microsomes as 0.85 ± 0.34 ml/min/kg microsomal protein. | 27 | |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 203.6 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 203.6 | ml/min/kg | true | 31 | unspecified_variation | null | null | in vivo | rat | null | null | null | 24616265 | 0.98 | q4 | hepatic | b73e1e55e4e19fd6ecb1317b09a2fdb701628d98e3e29a8c63f669acd7038ee1 | 760 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b73e1e55e4e19fd6ecb1317b09a2fdb701628d98e3e29a8c63f669acd7038ee1 | 7fe6b5650226b25c9ea3f6d87b0a7bcb998a62a302d805418451e1c25623f89b | Intravenous administration. | In vivo intravenous total clearance (CLint) for NVS‑CRF38 in rats was 203.6 ± 31.0 ml/min/kg. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 42.3 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 42.3 | ml/min/kg | true | 6.5 | unspecified_variation | null | null | in vivo | rat | null | null | null | 24616265 | 0.98 | q4 | hepatic | 33a051a07354259bb356c3d016001b5887008272ba60ce706fb2af2f43981937 | 761 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 33a051a07354259bb356c3d016001b5887008272ba60ce706fb2af2f43981937 | f9a25101ee41f4e89dfed236a1417d8fbe8223d054007e92d4d5b3c0852e4948 | Intravenous administration, O‑demethylation pathway. | The in vivo intravenous O‑demethylation clearance for NVS‑CRF38 in rats was 42.3 ± 6.5 ml/min/kg. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 24.9 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 24.9 | ml/min/kg | true | 1.6 | unspecified_variation | null | null | in vivo | rat | null | null | null | 24616265 | 0.98 | q4 | hepatic | f5acc48ca3aaed30c13effd85947157ea86e126ea397902dc8c94d6045027ed2 | 762 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f5acc48ca3aaed30c13effd85947157ea86e126ea397902dc8c94d6045027ed2 | 0d629e0b131979a75f0dab6a4f76b310f48d7ce5e0e379be1648ada994d93746 | Oral administration, O‑demethylation pathway. | The in vivo oral O‑demethylation clearance for NVS‑CRF38 in rats was 24.9 ± 1.6 ml/min/kg. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 5.7 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 5.7 | ml/min/kg | true | 0.5 | unspecified_variation | null | null | in vivo | rat | [13cd3] nvs-crf38 | null | null | 24616265 | 0.98 | q4 | hepatic | 4b59c9281b79ac5108a7362e4a1bd0cd4ff9e2728834fbe4aeebbb963b0b0039 | 763 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4b59c9281b79ac5108a7362e4a1bd0cd4ff9e2728834fbe4aeebbb963b0b0039 | a5c2c795144c1b4232f1df9cdf68d3b174ba8f5c03514842409023dcd2c3c311 | Intravenous administration, O‑demethylation pathway, deuterated form. | The in vivo intravenous O‑demethylation clearance for [13CD3] NVS‑CRF38 in rats was 5.7 ± 0.5 ml/min/kg. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 3.9 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 3.9 | ml/min/kg | true | 0.8 | unspecified_variation | null | null | in vivo | rat | [13cd3] nvs-crf38 | null | null | 24616265 | 0.98 | q4 | hepatic | cbadea1be8469944dbd788c79d2afbd0494570fee059330960827ba0a095d9c8 | 764 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | cbadea1be8469944dbd788c79d2afbd0494570fee059330960827ba0a095d9c8 | 012f7fe6eb22ba44892c72e4c4f3613096ef81e878470cbb237deb68b2852095 | Oral administration, O‑demethylation pathway, deuterated form. | The in vivo oral O‑demethylation clearance for [13CD3] NVS‑CRF38 in rats was 3.9 ± 0.8 ml/min/kg. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 203.6 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 203.6 | ml/min/kg | true | 31 | unspecified_variation | null | null | in vivo | rat (male sprague-dawley) | null | null | null | 24616265 | 0.96 | q4 | hepatic | 63d4e1e157bccc2bc19b716acc4264838b8df55efe16256757bc4a68d15d58ad | 765 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 63d4e1e157bccc2bc19b716acc4264838b8df55efe16256757bc4a68d15d58ad | 80f739751f0b9df907f865e4a75f8d3d92439f0c21788f1623bef15b5adf1952 | Total intrinsic clearance after i.v. dosing | Table in paragraph p:45 shows that the parent compound NVS-CRF38 has a total in vivo intrinsic clearance (CLint) of 203.6 ± 31.0 ml/min/kg after intravenous administration in male Sprague‑Dawley rats. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 42.3 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 42.3 | ml/min/kg | true | 6.5 | unspecified_variation | null | null | in vivo | rat (male sprague-dawley) | null | null | null | 24616265 | 0.96 | q4 | hepatic | 758fdd0bb5103666d9ffd95fdc4ef3f62b5ad3c266c8bb996fe9c5026dde05c2 | 766 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 758fdd0bb5103666d9ffd95fdc4ef3f62b5ad3c266c8bb996fe9c5026dde05c2 | defd2b167436705c1358c27fed0bbb62a7ce6f4e9eceda8f977b5d1cc54f50ca | O‑demethylation intrinsic clearance after i.v. dosing | Table in paragraph p:45 shows that the parent compound NVS-CRF38 has an O‑demethylation intrinsic clearance of 42.3 ± 6.5 ml/min/kg after intravenous administration in male Sprague‑Dawley rats. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 119.7 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 119.7 | ml/min/kg | true | 7.7 | unspecified_variation | null | null | in vivo | rat (male sprague-dawley) | null | null | null | 24616265 | 0.96 | q4 | hepatic | 38471a25e35177689ab2e9e21c5ca1be0b0b431122e7480ee285a52932fdaf25 | 767 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 38471a25e35177689ab2e9e21c5ca1be0b0b431122e7480ee285a52932fdaf25 | 66bf76b14a8fdcc960e7de0fa1d29464a83001d751e065adffc6f898b2aeee3f | Total intrinsic clearance after PO dosing | Table in paragraph p:45 reports that the parent compound NVS-CRF38 has a total in vivo intrinsic clearance (CLint) of 119.7 ± 7.7 ml/min/kg after oral (PO) administration in male Sprague‑Dawley rats. | 45 |
COc1ccc(-c2c(C)oc3c(-n4nc(C)nc4C)c(C)nn23)c(C)c1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 24.9 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 24.9 | ml/min/kg | true | 1.6 | unspecified_variation | null | null | in vivo | rat (male sprague-dawley) | null | null | null | 24616265 | 0.96 | q4 | hepatic | f42e847b1b90ec1e196aba42c5a438cff0f92291672c11071e1759a68e2cc5f0 | 768 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f42e847b1b90ec1e196aba42c5a438cff0f92291672c11071e1759a68e2cc5f0 | 65bda2537e141f5c74177df2602d083b7f26443f16d60bcc7d1c02b8915ca7ce | O‑demethylation intrinsic clearance after PO dosing | Table in paragraph p:45 indicates that the parent compound NVS-CRF38 has an O‑demethylation intrinsic clearance of 24.9 ± 1.6 ml/min/kg after oral (PO) administration in male Sprague‑Dawley rats. | 45 |
O=C1CN=C(c2ccccn2)c2cc(Br)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ml_min | 61.3 | ml/min | q4.hepatic_clearance.intrinsic_clearance.ml_min | hepatic_clearance | intrinsic_clearance | ml_min | null | null | null | dog | 61.3 | ml/min | false | null | null | null | null | in vivo species study | dog | null | null | null | 6107379 | 0.98 | q4 | hepatic | 420d6b986d54f8f3640660d27928afb0b750a631e99330923408f0625ea4576e | 772 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 420d6b986d54f8f3640660d27928afb0b750a631e99330923408f0625ea4576e | ebbe8d6779a2be759acabcecd7421682c573ea2d91c6e9656b1dd7d16ca442a6 | Value taken from Table II (dog data). | Table II reports that in dogs the intrinsic clearance (CLint) of bromazepam was 61.3 ml/min. | 39 |
O=C1CN=C(c2ccccn2)c2cc(Br)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ml_min | 81.6 | ml/min | q4.hepatic_clearance.intrinsic_clearance.ml_min | hepatic_clearance | intrinsic_clearance | ml_min | null | null | null | human | 81.6 | ml/min | false | null | null | null | null | in vivo species study | human | null | null | null | 6107379 | 0.98 | q4 | hepatic | bd13c7b430e4fe9b73991cd8b9627feaae76ff545997225ee99e84a66cef392e | 773 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bd13c7b430e4fe9b73991cd8b9627feaae76ff545997225ee99e84a66cef392e | b0919b1feb68ac365c9c4a5ec2af9f3db0b7ed8c6399c9cbbc45fbd1a4d0b2f0 | Value taken from Table II (human data). | Table II reports that in humans the intrinsic clearance (CLint) of bromazepam was 81.6 ml/min. | 39 |
O=C1CN=C(c2ccccn2)c2cc(Br)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_lw | 168 | ml/min/kg lw | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_lw | hepatic_clearance | intrinsic_clearance | ml_min_kg_lw | null | null | null | dog | 168 | ml/min/kg lw | false | null | null | null | null | in vivo species study | dog | null | null | null | 6107379 | 0.98 | q4 | hepatic | 4a86c49d2789abf12ef003972d69633ed03bba1a14714f63e6621b92bded919a | 774 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4a86c49d2789abf12ef003972d69633ed03bba1a14714f63e6621b92bded919a | 2e823e6f97c020abe958ba803fad3cb6070250b3f466fc3aa283a98a2c115e50 | Value taken from Table II (dog data). | Table II lists the intrinsic clearance per kilogram liver weight for bromazepam in dogs as 168.0 ml/min/kg LW. | 39 |
O=C1CN=C(c2ccccn2)c2cc(Br)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_lw | 40 | ml/min/kg lw | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg_lw | hepatic_clearance | intrinsic_clearance | ml_min_kg_lw | null | null | null | human | 40 | ml/min/kg lw | false | null | null | null | null | in vivo species study | human | null | null | null | 6107379 | 0.98 | q4 | hepatic | fdd823c79f58be9e11e2ded9cf57e52b2d085c578200588348127fb43196932b | 775 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fdd823c79f58be9e11e2ded9cf57e52b2d085c578200588348127fb43196932b | 7e13d8fbaee5fc396598e7f236d99bc0487a61f90022ea3a0635b155ff4b2cc8 | Value taken from Table II (human data). | Table II lists the intrinsic clearance per kilogram liver weight for bromazepam in humans as 40.0 ml/min/kg LW. | 39 |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.hepatic_clearance.ml_min | 8.2 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | rat | 8.2 | ml/min | true | 1.8 | unspecified_variation | null | null | isolated perfused rat liver (recirculating iprl) | rat | null | null | null | 9776356 | 0.96 | q4 | hepatic | e29e11fff860bdd3af92a0e47eeff2419b5fcf27539d1861f35f266ba042bd5e | 784 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e29e11fff860bdd3af92a0e47eeff2419b5fcf27539d1861f35f266ba042bd5e | 25609815fd5415330d5d67aa01765ea20ec44e89c97fab216a2de7e59745ca43 | Control (non‑infected) rats. | In the recirculating isolated perfused rat liver (IPRL) model, clearance of dihydroartemisinin (DHA) in control rats was a mean of 8.2 ± 1.8 ml min⁻¹ (n=8). | 1 |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.hepatic_clearance.ml_min | 6 | ml/min | q4.hepatic_clearance.hepatic_clearance.ml_min | hepatic_clearance | hepatic_clearance | ml_min | null | null | null | rat | 6 | ml/min | true | 1 | unspecified_variation | null | null | isolated perfused rat liver (recirculating iprl) | rat | null | null | malaria‐infected (p. berghei) rats | 9776356 | 0.96 | q4 | hepatic | c6169fbfa2c07b9c9dc59cfd498c5f0487cd468a5c414c57d78977c549e6aede | 785 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c6169fbfa2c07b9c9dc59cfd498c5f0487cd468a5c414c57d78977c549e6aede | f63d5ee250dd3c8557fd7fd885fd58717da85899abd2686898f0dedc78ca3c98 | In the same IPRL model, clearance of DHA in malaria‑infected (MI) rats was reduced to a mean of 6.0 ± 1.0 ml min⁻¹ (n=8). | 1 | |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 5.2 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 5.2 | ul/min/mg protein | true | 1.3 | unspecified_variation | null | null | hepatic microsomal studies | rat | null | null | null | 9776356 | 0.95 | q4 | hepatic | 9f916a5b85c1f471977443f1668057c2bd0221da9afddff4b5297105f17c17a3 | 786 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 9f916a5b85c1f471977443f1668057c2bd0221da9afddff4b5297105f17c17a3 | 0281d3ce81c7eccefb77da47d8323ee7686f8b40cc6479d880d76d22a737f90e | Control (non‑infected) rat liver microsomes. | Hepatic microsomal studies showed intrinsic metabolic clearance (Vmax/Km) for DHA of 5.2 ± 1.3 µl min⁻¹ mg⁻¹ in control rat livers (n=6). | 1 |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 2.5 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 2.5 | ul/min/mg protein | true | 1.4 | unspecified_variation | null | null | hepatic microsomal studies | rat | null | null | malaria‐infected (p. berghei) rat livers | 9776356 | 0.95 | q4 | hepatic | eabc3d0fe0e1330e66eba2d7acee061cbd152e893a8999051c278179647b96fc | 787 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | eabc3d0fe0e1330e66eba2d7acee061cbd152e893a8999051c278179647b96fc | 33b3c7a975c6187252ce1a0cf6892d0c30729889d9e1817a155e8e0fe5ee16bc | In malaria‑infected rat livers, the intrinsic metabolic clearance (Vmax/Km) for DHA was 2.5 ± 1.4 µl min⁻¹ mg⁻¹ (n=6). | 1 | |
CCCc1cc(CCC)c(OCC(O)CNC(C)C)c(CCC)c1 | q4.hepatic_metabolism.half_life.minute | 9.1 | min | q4.hepatic_metabolism.half_life.minute | hepatic_metabolism | half_life | minute | null | null | null | rat | 9.1 | min | true | 0.8 | unspecified_variation | null | null | recirculating isolated perfused rat liver (iprl) | rat | dha | null | control (non‐malaria‐infected) livers | 9776356 | 0.96 | q4 | hepatic | 25d2f3aa4b513ab1ab39d2a62509c560148d6e87bbd3b09a9afe525d25b8a279 | 791 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 25d2f3aa4b513ab1ab39d2a62509c560148d6e87bbd3b09a9afe525d25b8a279 | 76333af2db343cff6f88b58c11f4939119a5cef94f7b3697e11e5f6dae31a54c | The metabolic half‑life (t₁/₂) of DHA in control livers was 9.1 ± 0.8 min. | 43 | |
CCCc1cc(CCC)c(OCC(O)CNC(C)C)c(CCC)c1 | q4.hepatic_metabolism.half_life.minute | 12.1 | min | q4.hepatic_metabolism.half_life.minute | hepatic_metabolism | half_life | minute | null | null | null | rat | 12.1 | min | true | 1.9 | unspecified_variation | null | null | recirculating isolated perfused rat liver (iprl) | rat | dha | null | malaria‐infected (mi) livers | 9776356 | 0.96 | q4 | hepatic | 133925f7eacf7f29b25a301d861efeed33ac3da801d95c7c53fd8f2d94e7c271 | 792 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 133925f7eacf7f29b25a301d861efeed33ac3da801d95c7c53fd8f2d94e7c271 | e641b69c2462d300dc86d101423b0d8022bf6b43219b1f02a7b4fa44ba4bcf34 | The metabolic half‑life (t₁/₂) of DHA in malaria‑infected (MI) livers was 12.1 ± 1.9 min. | 43 | |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1_protein | 5.2 | ul min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ul_min_1_mg_1_protein | null | null | null | rat | 5.2 | ul min-1 mg-1 protein | true | 1.3 | unspecified_variation | null | null | rat liver microsomes | rat | null | null | null | 9776356 | 0.98 | q4 | hepatic | 42cd19d3ad1a49fa8aba8bdaa8fb53613c08fb3bdd7dda87956bcbd690293653 | 797 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 42cd19d3ad1a49fa8aba8bdaa8fb53613c08fb3bdd7dda87956bcbd690293653 | 802dbf9c2fe9bdef9964a1de6dcff74a5cffcd7d2c3ec778a1821e938a36f52c | Control (non‑malaria‑infected) rats. | Table 4 shows that in rat liver microsomal enzyme studies, the intrinsic metabolic clearance of DHA in control rats was 5.2 ± 1.3 µL min⁻¹ mg⁻¹ protein. | 59 |
C[C@@H]1CC[C@H]2[C@@H](C)C(O)O[C@@H]3O[C@@]4(C)CC[C@@H]1[C@]32OO4 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1_protein | 2.5 | ul min-1 mg-1 protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1_protein | hepatic_clearance | intrinsic_clearance | ul_min_1_mg_1_protein | null | null | null | rat | 2.5 | ul min-1 mg-1 protein | true | 1.4 | unspecified_variation | null | null | rat liver microsomes | rat | null | null | malaria‐infected (mi) rats | 9776356 | 0.98 | q4 | hepatic | c7110e3c1044204d338385b2a54bd5c161124efdbc04fb3dc57aa1c247dfda5e | 798 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c7110e3c1044204d338385b2a54bd5c161124efdbc04fb3dc57aa1c247dfda5e | eacc1c711f4972447b3c4596bf3b6a0c1a525dbde5c51116bf33a6fc9abef9c2 | Table 4 shows that in malaria‑infected rats, the intrinsic metabolic clearance of DHA measured in rat liver microsomes was 2.5 ± 1.4 µL min⁻¹ mg⁻¹ protein. | 59 | |
CCOc1ccc2nc3ccc(=O)cc-3oc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | 40 | ul min-1 mg-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_mg_1 | null | null | null | human | 40 | ul min-1 mg-1 | true | 3 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 12580989 | 0.98 | q4 | hepatic | e3fde18a3558fdf7e17b42707cde63166b9eb2e33ec733f990befaff647d861b | 804 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e3fde18a3558fdf7e17b42707cde63166b9eb2e33ec733f990befaff647d861b | 807ef6a09355a05a16e620718fb1f44d928230136a08237d7ce2da99e197517c | Table 1 reports that the intrinsic clearance (CLint) of ethoxyresorufin measured in pooled human liver microsomes (HLM) was 40 ± 3 µl·min⁻¹·mg⁻¹. | 29 | |
CCOc1ccc2nc3ccc(=O)cc-3oc2c1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | 0.6 | ul min-1 pmol-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_pmol_1 | null | null | null | human | 0.6 | ul min-1 pmol-1 | true | 0.2 | unspecified_variation | null | null | recombinant cyp1a2 | human | null | cyp1a2 | null | 12580989 | 0.98 | q4 | hepatic | 4b56b6e039191786173543e02d41c34415261d331cea302dedafadff189fb3a9 | 805 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4b56b6e039191786173543e02d41c34415261d331cea302dedafadff189fb3a9 | 74ecb2136f6768ebf65140e6448d2eab70c3b77538b39be9ecf32c46eb91688e | Table 1 shows that the intrinsic clearance (CLint) of ethoxyresorufin catalyzed by recombinant CYP1A2 was 0.6 ± 0.2 µl·min⁻¹·pmol⁻¹. | 29 | |
CC[C@@]1(c2ccccc2)NC(=O)N(C)C1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | 5 | ul min-1 mg-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_mg_1 | null | null | null | human | 5 | ul min-1 mg-1 | true | 1 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 12580989 | 0.98 | q4 | hepatic | 95972ed07c2fea12cc5c3bd1849862621145eb076d1b5bf1e50b434ffabdb249 | 808 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 95972ed07c2fea12cc5c3bd1849862621145eb076d1b5bf1e50b434ffabdb249 | c6245ece5b207432947a5118937d87c9b1cc6072fc747392f2e1e5a871685cec | Table 1 reports that the intrinsic clearance (CLint) of S-mephenytoin in pooled human liver microsomes was 5 ± 1 µl·min⁻¹·mg⁻¹. | 29 | |
CC[C@@]1(c2ccccc2)NC(=O)N(C)C1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | 0.66 | ul min-1 pmol-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_pmol_1 | null | null | null | human | 0.66 | ul min-1 pmol-1 | true | 0.12 | unspecified_variation | null | null | recombinant cyp2c19 | human | null | cyp2c19 | null | 12580989 | 0.98 | q4 | hepatic | 07d0da4c5af8ffa75704cbc4824fefe23200da8d266f45fec11540989bac6775 | 809 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 07d0da4c5af8ffa75704cbc4824fefe23200da8d266f45fec11540989bac6775 | 60149d53bcca123abac21c875c59e9e5f0cbbf12b1e2c087afc5f3fa6fb6a924 | Table 1 shows that the intrinsic clearance (CLint) of S-mephenytoin catalyzed by recombinant CYP2C19 was 0.66 ± 0.12 µl·min⁻¹·pmol⁻¹. | 29 | |
COc1ccc2c(c1)[C@]13CCCC[C@@H]1[C@H](C2)N(C)CC3 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | 22 | ul min-1 mg-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_mg_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_mg_1 | null | null | null | human | 22 | ul min-1 mg-1 | true | 1 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 12580989 | 0.98 | q4 | hepatic | 9fd26632a6332842eb6fe7a7695e20f8bb25f0ed7ffa1c6b589aaab082a72936 | 810 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 9fd26632a6332842eb6fe7a7695e20f8bb25f0ed7ffa1c6b589aaab082a72936 | d0b6809ff5402c256230c7cabf7834ec1569169199b0d97984f85bf191fb2e19 | Table 1 reports that the intrinsic clearance (CLint) of dextromethorphan in pooled human liver microsomes was 22 ± 1 µl·min⁻¹·mg⁻¹. | 29 | |
COc1ccc2c(c1)[C@]13CCCC[C@@H]1[C@H](C2)N(C)CC3 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | 1.97 | ul min-1 pmol-1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_1_pmol_1 | hepatic_clearance | intrinsic_clearance | ul_min_1_pmol_1 | null | null | null | human | 1.97 | ul min-1 pmol-1 | true | 0.2 | unspecified_variation | null | null | recombinant cyp2d6 | human | null | cyp2d6 | null | 12580989 | 0.98 | q4 | hepatic | 3a050c8c3cfd6048ec7d76d3a6b95e6a49db50c89a60d76d3d42b27988671053 | 811 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3a050c8c3cfd6048ec7d76d3a6b95e6a49db50c89a60d76d3d42b27988671053 | ef74ad599274f24cfa7841a8256c515e788dd3d6fab03a90b9107604fa1adc8f | Table 1 shows that the intrinsic clearance (CLint) of dextromethorphan catalyzed by recombinant CYP2D6 was 1.97 ± 0.20 µl·min⁻¹·pmol⁻¹. | 29 | |
COc1ccc(CCN(C)CCC[C@@](C#N)(c2ccc(OC)c(OC)c2)C(C)C)cc1OC | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 138 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 138 | ul/min/mg protein | true | 35 | unspecified_variation | null | null | human liver microsomes | human | null | null | null | 12580989 | 0.96 | q4 | hepatic | 167d263da6732ca5ea70bb6d789d89a680344ca546f168a91315fc5e6fcb2e1d | 816 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 167d263da6732ca5ea70bb6d789d89a680344ca546f168a91315fc5e6fcb2e1d | c5139e23f92ecfc194a90f4c70aad40bc688919dc061171593ef14131b7d9283 | Mean ± standard deviation from three experiments. | Table 5 lists the control HLM intrinsic clearance for verapamil as 138 ± 35 µL min⁻¹ mg⁻¹ protein (mean ± s.d., three experiments). | 35 |
CCOC(=O)N1CCC(=C2c3ccc(Cl)cc3CCc3cccnc32)CC1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 14.3 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 14.3 | ml/min/kg | true | 1.5 | unspecified_variation | null | null | prediction from cryopreserved human hepatocyte data | human | null | null | null | 23883428 | 0.96 | q4 | hepatic | 76b3c2ad6f6312a8421af8db9ea15ebc1f8181effedf58e7725ba2ed38873dd6 | 915 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 76b3c2ad6f6312a8421af8db9ea15ebc1f8181effedf58e7725ba2ed38873dd6 | 034a808a22cb8cbee2e77806daddff992ba7c87ddaec89426a5ce2ee0d60c81b | The predicted in vivo hepatic clearance (CLHp) for loratadine was 14.3 ± 1.5 mL/min/kg. | 48 | |
C=CC[C@@H]1C=C(C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC.O | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 23.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 23.9 | ml/min/kg | true | 11.2 | unspecified_variation | null | null | prediction from cryopreserved human hepatocyte data | human | null | null | null | 23883428 | 0.96 | q4 | hepatic | b187ed7e0d1b69c9ba8d89360ca9b859ee4137480d9c5d7fd71c99d1f582d6d9 | 917 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b187ed7e0d1b69c9ba8d89360ca9b859ee4137480d9c5d7fd71c99d1f582d6d9 | f5768a761b7987950d816ad4ffa019f5c55210741bba4fd8a9d0235f945354ba | The predicted in vivo hepatic clearance (CLHp) for tacrolimus was 23.9 ± 11.2 mL/min/kg. | 48 | |
CCOC(=O)N1CCC(=C2c3ccc(Cl)cc3CCc3cccnc32)CC1 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 14.3 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 14.3 | ml/min/kg | true | 1.5 | unspecified_variation | null | null | scaled from human hepatocyte suspension data | human | null | null | null | 23883428 | 0.95 | q4 | hepatic | 9b791b9163ad52ddd37d06bc111b23bf4f2637e8696ba92497a79a92f731a400 | 932 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 9b791b9163ad52ddd37d06bc111b23bf4f2637e8696ba92497a79a92f731a400 | a2d14902b91d9ba77b1680013a7f2b2a708ff86dbf69caf1c22b0a52d771fc1a | Prediction based on in‑vitro data assuming f_u,b/f_u,inc = 1; fmCYP3A was 0.50 in the same study. | For loratadine, the authors predicted a hepatic clearance of 14.3 ± 1.5 mL/min/kg with an fmCYP3A of 50%. | 58 |
C=CC[C@@H]1C=C(C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC.O | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 23.9 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | human | 23.9 | ml/min/kg | true | 11.2 | unspecified_variation | null | null | scaled from human hepatocyte suspension data | human | null | null | null | 23883428 | 0.94 | q4 | hepatic | 0491be7859cbe330cc1b7aabcf5d181865568153b8af02a3f90f6275460cc9a8 | 933 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 0491be7859cbe330cc1b7aabcf5d181865568153b8af02a3f90f6275460cc9a8 | 431cdf2c697f815b1781ee1e220b5708826812e21cb9a61d498c1db65aa04538 | Prediction assumes f_u,b/f_u,inc = 1; literature CLHp range 10–90 mL/min/kg. | The predicted hepatic clearance for tacrolimus was 23.9 ± 11.2 mL/min/kg. | 58 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 27.8 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 27.8 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.97 | q4 | hepatic | 95790bcdf5e761e395baea277870f79baeb75ab2d175414bffdd71ef28776ffc | 940 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 95790bcdf5e761e395baea277870f79baeb75ab2d175414bffdd71ef28776ffc | e4c13eb13af4c941f4b828c1bf5da8d5d5a05a27b95fa8f680e5e6ae53b1c1ce | Concentration: 0.1 µM. | Octocrylene showed an in vitro intrinsic clearance of 27.8 µl/min per million cells at 0.1 µM in human suspension hepatocytes. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 15.23 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 15.23 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.97 | q4 | hepatic | 84744d890bbb9d08995b054d30da7fe1c6c8be4768695199940ceb99a7851ce5 | 941 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 84744d890bbb9d08995b054d30da7fe1c6c8be4768695199940ceb99a7851ce5 | 3ffc0f9763886200accdec4759908218f306b73fc81090d6d295fd5851a25189 | Concentration: 1 µM. | Octocrylene showed an in vitro intrinsic clearance of 15.23 µl/min per million cells at 1 µM in human suspension hepatocytes. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 34 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 34 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.97 | q4 | hepatic | c98acd619f98031eef12379077c0cd546964ed0131ffe1cae558c2ba7e598fca | 942 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c98acd619f98031eef12379077c0cd546964ed0131ffe1cae558c2ba7e598fca | 29769761feb5a5f3ffea28af5d1dac328144b58ef82363c3d6bf207e3474b47e | Concentration: 0.1 µM. | 4‑MBC displayed an in vitro intrinsic clearance of 34.0 µl/min per million cells at 0.1 µM in human suspension hepatocytes. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 32.2 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 32.2 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.97 | q4 | hepatic | 75d8a6a5e1bb0eb7abdf9d0d92f0c9cbdea7020307d151a0200dbb337b1dab1a | 943 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 75d8a6a5e1bb0eb7abdf9d0d92f0c9cbdea7020307d151a0200dbb337b1dab1a | 40d9d791db6f67e474637476d67916b93cd96586e1ee13b7b5f94ea4f3e066c0 | Concentration: 1 µM. | 4‑MBC displayed an in vitro intrinsic clearance of 32.2 µl/min per million cells at 1 µM in human suspension hepatocytes. | 87 |
CCCCCCCCOC(=O)C(=Cc1ccccc1)OC | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 43.34 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | null | 43.34 | ul/min/million cells | false | null | null | null | null | in vitro cell-based assay (million cells) | null | null | null | null | 37584694 | 0.97 | q4 | hepatic | b5278b9326db76a133d5331c0e33421024c1c4172426d3302a6b7cc06c574f12 | 944 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b5278b9326db76a133d5331c0e33421024c1c4172426d3302a6b7cc06c574f12 | 550f70d4aa1050b0a36a9d7b338fe65f4a159fdd48e28a1fd45cc8193b9f8a3e | Values were obtained from Table (p:87) and represent the mean intrinsic clearance at 10 µM; scaling assumptions are described in p:86 (70 kg body weight, 1.5 kg liver, Q_liver 90 L/h). | The in vitro intrinsic clearance (CLint) for octinoxate (OMC) was reported as a mean of 43.34 µl/min per million cells, derived from the 10 µM concentration point in the table. | 87 |
CCCCCCCCOC(=O)C(=Cc1ccccc1)OC | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 43.34 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 43.34 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.96 | q4 | hepatic | 82a81ee50136aaf9077773a537b0ccf45118e96c625e3680af57b50dacfbec64 | 945 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 82a81ee50136aaf9077773a537b0ccf45118e96c625e3680af57b50dacfbec64 | 7743e99f82050d00f430fa803b0e33a6485f59b39a0a9ca6585366afa6108a8d | Value reported only for the 10 µM concentration; lower concentrations not measurable. | The in vitro intrinsic clearance for OMC measured in human suspension hepatocytes was 43.34 µl/min per million cells (value available only at the 10 µM concentration). | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 7.6 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 7.6 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.96 | q4 | hepatic | 6bea161d82d4dc1d1dad30dbbf85e7389b21c477c75337009fac2b4d1f7d583f | 946 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 6bea161d82d4dc1d1dad30dbbf85e7389b21c477c75337009fac2b4d1f7d583f | a44cde2a9254db9798d1d9f3e253f2570a44ea16baf2b711818367acf670a5d2 | Concentration: 10 µM; shows decreasing clearance with higher concentration, indicating saturation. | Octocrylene showed an in vitro intrinsic clearance of 7.6 µl/min per million cells at 10 µM in human suspension hepatocytes. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 23.8 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 23.8 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.96 | q4 | hepatic | 686b61be5f9a03cdd8c670e4b5ee78bba6f241a1dfc43f2b8fb58ca1435df2cf | 947 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 686b61be5f9a03cdd8c670e4b5ee78bba6f241a1dfc43f2b8fb58ca1435df2cf | c6ce277767a6038d3be9f03d1bcc4387d56394b7a8202fd05de6dc5e8d7cefff | Concentration: 10 µM; decreasing clearance with higher concentration indicates saturation. | 4‑MBC displayed an in vitro intrinsic clearance of 23.8 µl/min per million cells at 10 µM in human suspension hepatocytes. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 30 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | null | 30 | ul/min/million cells | false | null | null | null | null | in vitro cell-based assay (million cells) | null | null | null | null | 37584694 | 0.96 | q4 | hepatic | 2c65729f120edd94cf586d986be8d6681aed6a05bbaaae87f958a04723b14ba2 | 948 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 2c65729f120edd94cf586d986be8d6681aed6a05bbaaae87f958a04723b14ba2 | 854ffd553f1878aee604d0de325eb5c9bc406de83b3678bef8e09fc13ecd9416 | Mean derived from 0.1 µM, 1 µM, and 10 µM data points (p:87). | 4-Methoxibenzophenone (4‑MBC) exhibited a mean in vitro intrinsic clearance of 30.0 µl/min per million cells. | 87 |
CCCCCCCCOC(=O)C(=Cc1ccccc1)OC | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | 1.1 | l/h/kg bw | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | hepatic_clearance | hepatic_clearance | l_h_kg_bw | null | null | null | human | 1.1 | l/h/kg bw | false | null | null | null | null | scaled in vivo using well‐stirred liver model (equation 2) | human | null | null | null | 37584694 | 0.95 | q4 | hepatic | d240b240bf6efe2d79fe095766658418aaf97ea3d98354db5156869a53620642 | 949 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | d240b240bf6efe2d79fe095766658418aaf97ea3d98354db5156869a53620642 | 011498da1023b745d5e53f67b77e8b29dfdab94cc74fefa9b4b5aa04aa7681eb | Derived from in vitro CLint scaled to 312.0 l/h/kg liver. | For OMC, the in vivo hepatic clearance (CL liver) calculated with the non‑restrictive well‑stirred model (equation 2) was 1.1 l/h per kg body weight. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 16.9 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 16.9 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.95 | q4 | hepatic | e9fd1d0fae74b2cef5b1b86fe18005d48c14b03e5b27c346fe3a607ca4bffec1 | 950 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e9fd1d0fae74b2cef5b1b86fe18005d48c14b03e5b27c346fe3a607ca4bffec1 | ba47a45a0791ec2c6c00cb9849e72dd4a4c8d0c95b677823b90ffb71c9cce088 | Mean of values at 0.1, 1, and 10 µM. | The mean in vitro intrinsic clearance for octocrylene across the three tested concentrations was 16.9 µl/min per million cells. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | 0.9 | l/h/kg bw | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | hepatic_clearance | hepatic_clearance | l_h_kg_bw | null | null | null | human | 0.9 | l/h/kg bw | false | null | null | null | null | scaled in vivo using well‐stirred liver model (equation 2) | human | null | null | null | 37584694 | 0.95 | q4 | hepatic | 947c540197bb7c4cc29baa4efe109b6c3ad12de27bcbb46651f9b7736e4fbf3e | 951 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 947c540197bb7c4cc29baa4efe109b6c3ad12de27bcbb46651f9b7736e4fbf3e | bcb962747e732e676c78e3cae59b389beda3cad2eac5c0ca7e5a6697b8b85d34 | Derived from in vivo CLint scaled to 121.7 l/h/kg liver. | Octocrylene hepatic clearance (CL liver) calculated with equation 2 was 0.9 l/h per kg body weight. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 30 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | human | 30 | ul/min/million cells | false | null | null | null | null | human suspension hepatocytes | human | null | null | null | 37584694 | 0.95 | q4 | hepatic | 40fe0f34c66e5d781116b613d9e459f0ddaa858390bee928e4c1740a46f56fd2 | 952 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 40fe0f34c66e5d781116b613d9e459f0ddaa858390bee928e4c1740a46f56fd2 | ceb73a289c0f25189d8f67009c855059962900d8936d4b373cc5ef4b2c196f14 | Mean of values at 0.1, 1, and 10 µM. | The mean in vitro intrinsic clearance for 4‑MBC across the three tested concentrations was 30.0 µl/min per million cells. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | 1 | l/h/kg bw | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | hepatic_clearance | hepatic_clearance | l_h_kg_bw | null | null | null | human | 1 | l/h/kg bw | false | null | null | null | null | scaled in vivo using well‐stirred liver model (equation 2) | human | null | null | null | 37584694 | 0.95 | q4 | hepatic | f3496eb163579fc69e4e434602ba37789588e2e170881cdc1746413de635ba2c | 953 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | f3496eb163579fc69e4e434602ba37789588e2e170881cdc1746413de635ba2c | ee47e59eebed1ef88d2aba4c779a7382ca12b293f7e9d00c2b3bbc70ee293f1b | Derived from in vivo CLint scaled to 216 l/h/kg liver. | 4‑MBC hepatic clearance (CL liver) calculated with equation 2 was 1.0 l/h per kg body weight. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | 16.9 | ul/min/million cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_million_cells | hepatic_clearance | intrinsic_clearance | ul_min_million_cells | null | null | null | null | 16.9 | ul/min/million cells | false | null | null | null | null | in vitro cell-based assay (million cells) | null | null | null | null | 37584694 | 0.95 | q4 | hepatic | ad2dd0937179832f1ed7f6596a0ae21fa5dd8a928400300db36aa990c1071eed | 954 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | ad2dd0937179832f1ed7f6596a0ae21fa5dd8a928400300db36aa990c1071eed | 533c1a44e5ea1534f7e5797e877200ad2756986eeaf96bfbb6c5789cba447923 | Mean calculated from 0.1 µM, 1 µM, and 10 µM data points (p:87). | Octocrylene showed a mean in vitro intrinsic clearance of 16.9 µl/min per million cells across the tested concentrations. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.intrinsic_clearance.l_h_kg_liver | 121.7 | l/h/kg liver | q4.hepatic_clearance.intrinsic_clearance.l_h_kg_liver | hepatic_clearance | intrinsic_clearance | l_h_kg_liver | null | null | null | null | 121.7 | l/h/kg liver | false | null | null | null | null | scaled from in vitro data | null | null | null | null | 37584694 | 0.95 | q4 | hepatic | 5c49c194021bcfce4d22eb519726f79fbef6371ea3a2baa3fa3209e4692df10d | 955 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 5c49c194021bcfce4d22eb519726f79fbef6371ea3a2baa3fa3209e4692df10d | 96087a141176d129d8059b471a2b5b91462bffd0a04b5c257b65046513beb9c2 | Scaling based on assumptions described in p:86 (70 kg body weight, 1.5 kg liver, Q_liver = 90 L/h). | Octocrylene had an in vivo scaled intrinsic clearance of 121.7 l/h per kg liver. | 87 |
CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | 0.9 | l/h/kg bw | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | hepatic_clearance | hepatic_clearance | l_h_kg_bw | null | null | null | null | 0.9 | l/h/kg bw | false | null | null | null | null | in vivo scaled calculation | null | null | null | null | 37584694 | 0.95 | q4 | hepatic | 235c03bf6c0ead6941320a12f30da2a999504f5ab5da15d9d3de6410d0af0376 | 956 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 235c03bf6c0ead6941320a12f30da2a999504f5ab5da15d9d3de6410d0af0376 | 9b65e5c22cc2b845ce8e348726408a84c6ed04af75c622fc0d181e6dc8df65a5 | Derived using Equation 2 with the standard scaling assumptions (p:86). | The hepatic clearance (CL liver) for octocrylene was calculated as 0.9 l/h per kg body weight. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.intrinsic_clearance.l_h_kg_liver | 216 | l/h/kg liver | q4.hepatic_clearance.intrinsic_clearance.l_h_kg_liver | hepatic_clearance | intrinsic_clearance | l_h_kg_liver | null | null | null | null | 216 | l/h/kg liver | false | null | null | null | null | scaled from in vitro data | null | null | null | null | 37584694 | 0.95 | q4 | hepatic | 44446a1de82da294a1eaaeb5049bce8930a234d1bdab7a9329c5cdbc86ca4a4c | 957 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 44446a1de82da294a1eaaeb5049bce8930a234d1bdab7a9329c5cdbc86ca4a4c | 80d3344d9cab0a571e80dec6ec89118896592acc1dee78eec3b712a06b22e4e3 | Scaling based on the assumptions stated in p:86 (70 kg body weight, 1.5 kg liver, Q_liver = 90 L/h). | The scaled in vivo intrinsic clearance for 4‑MBC was 216 l/h per kg liver. | 87 |
Cc1ccc(C=C2C(=O)C3(C)CCC2C3(C)C)cc1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | 1 | l/h/kg bw | q4.hepatic_clearance.hepatic_clearance.l_h_kg_bw | hepatic_clearance | hepatic_clearance | l_h_kg_bw | null | null | null | null | 1 | l/h/kg bw | false | null | null | null | null | in vivo scaled calculation | null | null | null | null | 37584694 | 0.95 | q4 | hepatic | 20f145249b25dc5265f3a98d2b570a466d682058e559be7240b10c9f7b64e6ae | 958 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 20f145249b25dc5265f3a98d2b570a466d682058e559be7240b10c9f7b64e6ae | 2d7fd0c6e691a96de31984fef719dd12e96af52a54dfd22b6059218c4c579976 | Derived using Equation 2 with standard scaling parameters (p:86). | The hepatic clearance (CL liver) for 4‑MBC was calculated as 1.0 l/h per kg body weight. | 87 |
COCCO | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 0.62 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 0.62 | ul/min/mg | false | null | null | null | null | human hepatocytes | human | egme | null | null | 39655648 | 0.97 | q4 | hepatic | a000852adf3f5d86eb99e4193e7d384808750715e75080b919ca4b93151c38ea | 996 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a000852adf3f5d86eb99e4193e7d384808750715e75080b919ca4b93151c38ea | d08dc6a45a6c5538a23a851875f7e73088f4cff4de6688691d2af80914d85623 | Classified as low clearance based on scaling factors. | Aligning our results with an existing study performed on EGME using human hepatocytes, we report a K_m of 1700 µM and V_max of 61.3 nmol/h/10^6 cells, which yields a calculated in vitro intrinsic clearance (CL_int) of 0.62 µL/min/mg after applying the scaling factors from our study. This value is classified as a low cl... | 100 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.6 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 0.6 | ul/min/mg protein | false | null | null | null | null | rat in vitro hepatic metabolism (cyp450) | rat | null | cyp450 | null | 24118734 | 0.98 | q4 | hepatic | 5c60310ccf27d86a2e955556089fb13244d4186128b443d46b18d9284c8c7657 | 997 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 5c60310ccf27d86a2e955556089fb13244d4186128b443d46b18d9284c8c7657 | 66132694f08031958c8d16d8fadef00c1387e064ec8ba94b05b871845e0efb32 | In vitro, the intrinsic clearance (Clint) of rhein in cytochrome P450 (CYP450) metabolism of rat was 0.6 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 7.8 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 7.8 | ul/min/mg protein | false | null | null | null | null | rat in vitro hepatic metabolism (ugt) | rat | null | ugt | null | 24118734 | 0.98 | q4 | hepatic | 090302736ba14f59fc03c24ff5ef639b564acdb262e41eb35ca1aa9087fc3b59 | 998 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 090302736ba14f59fc03c24ff5ef639b564acdb262e41eb35ca1aa9087fc3b59 | bb5e9fdec8be155e404277b6004233f77ee2d42dc5416a4ab71c73a2ee4c2649 | In vitro, the intrinsic clearance (Clint) of rhein in UDP-glucuronosyltransferase (UGT) metabolism of rat was 7.8 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 5.5 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 5.5 | ul/min/mg protein | false | null | null | null | null | rat in vitro hepatic metabolism (sult) | rat | null | sult | null | 24118734 | 0.98 | q4 | hepatic | 139e6708c84f5abdfebec4051cf430e2b34f813d5633bc3ccd9934768e71221c | 999 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 139e6708c84f5abdfebec4051cf430e2b34f813d5633bc3ccd9934768e71221c | 70808fefb47fa657053a187f65d5cdd690e0949a2372f706109c17ad248ee547 | In vitro, the intrinsic clearance (Clint) of rhein in sulfotransferase (SULT) metabolism of rat was 5.5 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.1 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.1 | ul/min/mg protein | false | null | null | null | null | human in vitro hepatic metabolism (cyp450) | human | null | cyp450 | null | 24118734 | 0.98 | q4 | hepatic | 4a7e30dd5ceafa54b6b45442332ee448b2cf4592ea3d8631e643eec192af12aa | 1,000 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 4a7e30dd5ceafa54b6b45442332ee448b2cf4592ea3d8631e643eec192af12aa | 49ea4d7b649253f1f2b08ea5c28e193d2c87ee98310efe6a17b472d37cf076c0 | The Clint of rhein in CYP450 metabolism of human beings was 0.10 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 1.36 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 1.36 | ul/min/mg protein | false | null | null | null | null | human in vitro hepatic metabolism (ugt) | human | null | ugt | null | 24118734 | 0.98 | q4 | hepatic | 1a3c70c5e17c1cbfa0862629ea6ceef7a2403992368d120185b53ae68b82681b | 1,001 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1a3c70c5e17c1cbfa0862629ea6ceef7a2403992368d120185b53ae68b82681b | 1f8c56c3fef42495dbf621ffc96654059e98cd9be06f02c7063f49bdf6fc269f | The Clint of rhein in UGT metabolism of human beings was 1.36 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.68 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.68 | ul/min/mg protein | false | null | null | null | null | human in vitro hepatic metabolism (sult) | human | null | sult | null | 24118734 | 0.98 | q4 | hepatic | 8948143d4fc6ff0d6b239eefdf0717a18a889b0cedfea0ee49475bb73bfb314e | 1,002 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8948143d4fc6ff0d6b239eefdf0717a18a889b0cedfea0ee49475bb73bfb314e | ff73c532c45bbeaef9d2be00677af99e91e9a2cfc6cd6c52d1f6fd6ce9d43ec8 | The Clint of rhein in SULT metabolism of human beings was 0.68 µl/min/mg protein. | 0 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.6 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 0.6 | ul/min/mg protein | true | 0.09 | unspecified_variation | null | null | in vitro microsomal assay | rat | null | cyp450 | null | 24118734 | 0.96 | q4 | hepatic | 3ec248b78a96a324b9bb2f163bd1acfa7becae795d8121001e68073e066659f4 | 1,003 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 3ec248b78a96a324b9bb2f163bd1acfa7becae795d8121001e68073e066659f4 | eed8dfda84fc69d4f57b2ff6e656f9f1e94c86d16363313ff9b1a884b8af3c17 | Table 37 reports the in vitro intrinsic clearance (Clint) of rhein mediated by CYP450 in rat liver microsomes as 0.60 ± 0.09 µl/min/mg protein. | 37 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.1 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.1 | ul/min/mg protein | true | 0.02 | unspecified_variation | null | null | in vitro microsomal assay | human | null | cyp450 | null | 24118734 | 0.96 | q4 | hepatic | 20557d809e21815cd938273a8c4d04f9aeca854058fc6a69a4888d96af54baac | 1,004 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 20557d809e21815cd938273a8c4d04f9aeca854058fc6a69a4888d96af54baac | 1c38203c90318d675b6fe5f02b3d9e01ad67eca416c31b3d73b03178c77cb56d | Table 37 reports the in vitro intrinsic clearance (Clint) of rhein mediated by CYP450 in human liver microsomes as 0.10 ± 0.02 µl/min/mg protein. | 37 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 7.8 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 7.8 | ul/min/mg protein | true | 1.94 | unspecified_variation | null | null | in vitro microsomal assay | rat | null | ugt | null | 24118734 | 0.95 | q4 | hepatic | cf75707bdf2db20b6d65c64c107d55997d803aaec155226e46f3ad320db921b8 | 1,005 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | cf75707bdf2db20b6d65c64c107d55997d803aaec155226e46f3ad320db921b8 | 72be6d79ce370aba514f132815e9b441edd0da9ee0179f32c841a1928075ddd7 | Table 37 reports the in vitro intrinsic clearance (Clint) of rhein mediated by UGT in rat liver microsomes as 7.8 ± 1.94 µl/min/mg protein. | 37 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 1.36 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 1.36 | ul/min/mg protein | true | 0.22 | unspecified_variation | null | null | in vitro microsomal assay | human | null | ugt | null | 24118734 | 0.95 | q4 | hepatic | 465065d9cd812e9e9f2db072a37982f64a4e134cc85eab5c8d49a7e252e34894 | 1,006 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 465065d9cd812e9e9f2db072a37982f64a4e134cc85eab5c8d49a7e252e34894 | 2a0ee3f5fee38d7202f7279093e6b5c77eb1073858297224c4362a74b759a373 | Table 37 reports the in vitro intrinsic clearance (Clint) of rhein mediated by UGT in human liver microsomes as 1.36 ± 0.22 µl/min/mg protein. | 37 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 5.5 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 5.5 | ul/min/mg protein | true | 1.21 | unspecified_variation | null | null | in vitro microsomal assay | rat | null | sult | null | 24118734 | 0.95 | q4 | hepatic | 657a5b71dc0cf9185310c53b91785930501bfc4b1bca77313c14faf5c357957a | 1,007 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 657a5b71dc0cf9185310c53b91785930501bfc4b1bca77313c14faf5c357957a | 2dcde4a19f9b3260b15c28682af347f558b29a7161970e3262d10a1e4f5073cc | Table 37 reports the in vitro intrinsic clearance (Clint) of rhein mediated by SULT in rat liver microsomes as 5.5 ± 1.21 µl/min/mg protein. | 37 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.6 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 0.6 | ul/min/mg protein | true | 0.09 | unspecified_variation | null | null | in vitro liver microsomes | rat | null | cyp450 | null | 24118734 | 0.9 | q4 | hepatic | b42184556c88e331d55bc12b429f849268e8899184bf21a47b7e7d1d78f210ea | 1,008 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b42184556c88e331d55bc12b429f849268e8899184bf21a47b7e7d1d78f210ea | 5fd25aa5d619f60092a3cd4aa152bf11e06102d8986c8a1f6d0e9fe35067b496 | Mean ± standard deviation reported. | Table 3 reports the in‑vitro intrinsic clearance of rhein mediated by CYP450 enzymes as 0.60 ± 0.09 µL/min/mg protein in rat and 0.10 ± 0.02 µL/min/mg protein in human. | 37 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.1 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.1 | ul/min/mg protein | true | 0.02 | unspecified_variation | null | null | in vitro liver microsomes | human | null | cyp450 | null | 24118734 | 0.9 | q4 | hepatic | 602fd02be75bfb1e541aef8554c9d829ab382e86c6a9a5ebd734adb8b60d58cf | 1,009 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 602fd02be75bfb1e541aef8554c9d829ab382e86c6a9a5ebd734adb8b60d58cf | f91c14cefc8fdc4c7fea313581b248566aafb58ea5624cfeb23604b63dd3da1d | Mean ± standard deviation reported. | Table 3 reports the in‑vitro intrinsic clearance of rhein mediated by CYP450 enzymes as 0.60 ± 0.09 µL/min/mg protein in rat and 0.10 ± 0.02 µL/min/mg protein in human. | 37 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 7.8 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 7.8 | ul/min/mg protein | true | 1.94 | unspecified_variation | null | null | in vitro liver microsomes | rat | null | ugt | null | 24118734 | 0.9 | q4 | hepatic | cb1735ce6c7050157040e2c17e8824919187ff68275f7ce7d9c947ed8f39f76b | 1,010 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | cb1735ce6c7050157040e2c17e8824919187ff68275f7ce7d9c947ed8f39f76b | 65606fabac3ca030ee66331a32306c20082108b6b2f877c5782e421ac49a47d5 | Mean ± standard deviation reported. | Table 3 reports the in‑vitro intrinsic clearance of rhein mediated by UGT enzymes as 7.8 ± 1.94 µL/min/mg protein in rat and 1.36 ± 0.22 µL/min/mg protein in human. | 37 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.6 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 0.6 | ul/min/mg protein | true | 0.09 | unspecified_variation | null | null | liver microsomes | rat | null | cyp450 | null | 24118734 | 0.97 | q4 | hepatic | ae26140e630459e36cfb345d4eabb77c64dd9e18cb4ad020d049f3f80fc83783 | 1,011 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | ae26140e630459e36cfb345d4eabb77c64dd9e18cb4ad020d049f3f80fc83783 | 8b915d49427871229132cf194276ce59947f7c5588784fba8d421fa3a56cebb6 | In vitro intrinsic clearance measured in rat liver microsomes for CYP450-mediated oxidation of rhein. | In rat liver microsomes, the in vitro intrinsic clearance (CLint,vitro) of rhein mediated by CYP450 enzymes was reported as 0.60 ± 0.09 µl/min/mg protein. | 51 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.1 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.1 | ul/min/mg protein | true | 0.02 | unspecified_variation | null | null | liver microsomes | human | null | cyp450 | null | 24118734 | 0.97 | q4 | hepatic | b080d808c069f01251efc7f269d3b9581fa2c048f713d952cd755bb383038d30 | 1,012 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | b080d808c069f01251efc7f269d3b9581fa2c048f713d952cd755bb383038d30 | 0ca4faad9defe2eb9cdb6538015b237bdbd082a39c650e8f7b3ddb35a7b3f7bd | In vitro intrinsic clearance measured in human liver microsomes for CYP450-mediated oxidation of rhein. | In human liver microsomes, the in vitro intrinsic clearance (CLint,vitro) of rhein mediated by CYP450 enzymes was reported as 0.10 ± 0.02 µl/min/mg protein. | 51 |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 5.5 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | rat | 5.5 | ul/min/mg protein | true | 1.21 | unspecified_variation | null | null | in vitro | rat | null | sult | null | 24118734 | 0.95 | q4 | hepatic | c89de568eb3e1ec95014a8405f39057b0357863c0be1045625c77862ed6d060c | 1,015 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c89de568eb3e1ec95014a8405f39057b0357863c0be1045625c77862ed6d060c | 45351aaaec4c89060ca62f325d2869283b8f99a62bc44d11a84218588beb668d | For SULT metabolism, the in‑vitro intrinsic clearance (CLint,vitro) of rhein was 5.5 ± 1.21 µL/min/mg protein in rat and 0.68 ± 0.13 µL/min/mg protein in human. | 52 | |
O=C(O)c1cc(O)c2c(c1)C(=O)c1cccc(O)c1C2=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | 0.68 | ul/min/mg protein | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_protein | hepatic_clearance | intrinsic_clearance | ul_min_mg_protein | null | null | null | human | 0.68 | ul/min/mg protein | true | 0.13 | unspecified_variation | null | null | in vitro | human | null | sult | null | 24118734 | 0.95 | q4 | hepatic | a31d4926bc7d0653bfd5494b4622924e00dfa1b70cec958d1539062d3eb49f03 | 1,016 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | a31d4926bc7d0653bfd5494b4622924e00dfa1b70cec958d1539062d3eb49f03 | 6c564698da1bb0fa8cccfb224553cde60ae235221bf74fb9a65c1792f85ef77f | For SULT metabolism, the in‑vitro intrinsic clearance (CLint,vitro) of rhein was 5.5 ± 1.21 µL/min/mg protein in rat and 0.68 ± 0.13 µL/min/mg protein in human. | 52 | |
CC[C@@]1(c2ccccc2)NC(=O)N(C)C1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_cyp | 0.49 | ul/min/pmol cyp | q4.hepatic_clearance.intrinsic_clearance.ul_min_pmol_cyp | hepatic_clearance | intrinsic_clearance | ul_min_pmol_cyp | null | null | null | human | 0.49 | ul/min/pmol cyp | false | null | null | null | null | recombinant cyp (rhcyp) | human | parent drug | cyp2c19 | null | 29176011 | 0.98 | q4 | hepatic | bdae330bf7568c520b0a93839751db8a58f3c4ad6cb34cc26fb1a16c79bdb413 | 1,026 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | bdae330bf7568c520b0a93839751db8a58f3c4ad6cb34cc26fb1a16c79bdb413 | 25ebdd21b6e57699e9256cfe72a7d979510b3b9389e57908dbf5509b264b947d | CLint calculated based on total substrate concentrations without fu(mic) correction (see paragraph 51). | Table 2 (paragraph 52) reports that (S)-(+)-mephenytoin incubated with recombinant CYP2C19 gave an intrinsic clearance (CLint) of 0.49 µL/min/pmol CYP. | 52 |
CC[C@@]1(c2ccccc2)NC(=O)N(C)C1=O | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | 6.79 | ul/min/mg | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg | hepatic_clearance | intrinsic_clearance | ul_min_mg | null | null | null | human | 6.79 | ul/min/mg | false | null | null | null | null | human liver microsomes (hlm) | human | parent drug | cyp2c19 | null | 29176011 | 0.98 | q4 | hepatic | 8ace613ed9c5c41d6d9e26d05aecba583e84391752c1d19638f30cfe7bd87ede | 1,027 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8ace613ed9c5c41d6d9e26d05aecba583e84391752c1d19638f30cfe7bd87ede | f1efcb40373632d3e83f68ea5df33a860d786f0b4bf8a60a8a82aa24dc1001ae | CLint calculated based on total substrate concentrations without fu(mic) correction (see paragraph 51). | The same table shows that (S)-(+)-mephenytoin incubated with human liver microsomes gave an intrinsic clearance (CLint) of 6.79 µL/min/mg protein. | 52 |
O=C1[C@H](CC[C@H](O)c2ccc(F)cc2)[C@@H](c2ccc(O)cc2)N1c1ccc(F)cc1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 4,500 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 4,500 | ml/min/kg | false | null | null | null | null | rat liver microsomes (rlms) glucuronidation assay | rat | null | ugt | null | 21727754 | 0.99 | q4 | hepatic | 006f0c444e7d31d32761fbdb1a64987de1c537479b817238c49f5b18b7a3500b | 1,083 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 006f0c444e7d31d32761fbdb1a64987de1c537479b817238c49f5b18b7a3500b | dc9ceaf219ddbf639179d29c00b04044f29ee3b6be1a95a0cd2644b1f499a924 | In vitro CLint value reported as the upper end of the range for ezetimibe. | Table 3 shows that the in vitro intrinsic clearance (CLint) in rat liver microsomes ranged from 0.10 ml/min/kg for zidovudine to 4500 ml/min/kg for ezetimibe. | 28 |
O=C1[C@H](CC[C@H](O)c2ccc(F)cc2)[C@@H](c2ccc(O)cc2)N1c1ccc(F)cc1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 9,600 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | rat | 9,600 | ml/min/kg | false | null | null | null | null | rat liver microsomes (rlms) glucuronidation assay | rat | unbound | ugt | null | 21727754 | 0.99 | q4 | hepatic | 7ef582ff3ae9572899b2eeaa6a837a354cf5bf8724b7e62d88f4f8ceef130432 | 1,085 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 7ef582ff3ae9572899b2eeaa6a837a354cf5bf8724b7e62d88f4f8ceef130432 | 43425f39c82e8e2e314ce084718f62e4dd01eb7c6b021424f6f966e503c0fc13 | Unbound intrinsic clearance (CLuint) for ezetimibe. | Table 3 also gives unbound intrinsic clearance (CLuint) values ranging from 0.11 ml/min/kg for zidovudine to 9600 ml/min/kg for ezetimibe. | 28 |
O=C1[C@H](CC[C@H](O)c2ccc(F)cc2)[C@@H](c2ccc(O)cc2)N1c1ccc(F)cc1 | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 9,000 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | null | 9,000 | ml/min/kg | false | null | null | null | null | in vivo pharmacokinetic study | null | null | null | null | 21727754 | 0.98 | q4 | hepatic | 1f883fe700d37852a4626f186919b88e7ad68f24434d6dc1280419ce853718dd | 1,087 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1f883fe700d37852a4626f186919b88e7ad68f24434d6dc1280419ce853718dd | 17cc8dea91715ee570cfd647f1a55a2bdbc97d2a63a0a70b670fe190da8297b8 | In vivo CLint value reported as the high end of the range for ezetimibe. | In vivo intrinsic clearance (CLint) values determined using Eqs. 5–9 ranged from 5.7 ml/min/kg for zidovudine to 9000 ml/min/kg for ezetimibe. | 29 |
O=C(Cc1ccccc1Nc1c(Cl)cccc1Cl)O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O | q4.hepatic_metabolism.half_life.minute | 148 | min | q4.hepatic_metabolism.half_life.minute | hepatic_metabolism | half_life | minute | null | null | null | human | 148 | min | false | null | null | null | null | human liver microsomes | human | diclofenac ag | cyp (oxidative) | null | 12438516 | 0.95 | q4 | hepatic | 8d9138def2febab480144320364a052c0e29364f31a1317f55b4d4a2ec4738dd | 1,122 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 8d9138def2febab480144320364a052c0e29364f31a1317f55b4d4a2ec4738dd | ddf6b4218bb9aa2ac984643a379930a442171a561e9f687b877ecaf1587ebb61 | Half‑life derived after correcting for spontaneous hydrolysis; NADPH‑regenerating system present. | An in‑vitro metabolic half‑life of 148 min for diclofenac acyl glucuronide (diclofenac AG) disappearance due to oxidative metabolism in human liver microsomes was calculated (paragraph 45). | 45 |
O=C(Cc1ccccc1Nc1c(Cl)cccc1Cl)O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 5.5 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | human | 5.5 | ml/min/kg | false | null | null | null | null | scaled human liver | human | diclofenac ag | cyp (oxidative) | null | 12438516 | 0.94 | q4 | hepatic | 76fc40104e174cdc2f0c386eda04738431283a74545bdabb5edb06d4d51f870b | 1,123 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 76fc40104e174cdc2f0c386eda04738431283a74545bdabb5edb06d4d51f870b | 117a6bdf1e38eeeccd276e778d8d110e776d07e07e9bae8b41d64e2784cd73f9 | Extrapolated using equations 2 and 4 and previously described scaling factors. | From the in‑vitro t1/2 of 148 min, whole‑liver intrinsic clearance for oxidative metabolism of diclofenac AG (CLint,AG) was estimated as 5.5 ml/min/kg (paragraph 45). | 45 |
O=C(Cc1ccccc1Nc1c(Cl)cccc1Cl)O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 5.5 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | human | 5.5 | ml/min/kg | false | null | null | null | null | human liver microsomes (hlm) with nadph-regenerating system, t1/2 approach | human | acyl glucuronide | null | null | 12438516 | 0.96 | q4 | hepatic | 47b06f17490057ba124e5dc16dbdb3f89e1b4cb066894794d6b65e37ae37f1c3 | 1,126 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 47b06f17490057ba124e5dc16dbdb3f89e1b4cb066894794d6b65e37ae37f1c3 | 4880120d198afe9a295c5527b770946be1d76312e2dde5540f8ab2604401b9c9 | Estimate reflects oxidative metabolism of diclofenac acyl glucuronide (AG) after correction for its spontaneous hydrolysis. | Using an in vitro t1/2 approach after correcting for the spontaneous hydrolysis of diclofenac acyl glucuronide (AG) in human liver microsomal incubations, the authors estimated a hepatic intrinsic clearance of 5.5 ml/min/kg for the oxidative metabolism of diclofenac AG (CLint,AG). | 54 |
O=C(Cc1ccccc1Nc1c(Cl)cccc1Cl)O[C@@H]1O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]1O | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | 5.5 | ml/min/kg | q4.hepatic_clearance.intrinsic_clearance.ml_min_kg | hepatic_clearance | intrinsic_clearance | ml_min_kg | null | null | null | human | 5.5 | ml/min/kg | false | null | null | null | null | null | human | null | null | null | 12438516 | 0.96 | q4 | hepatic | be3642f5581a84f836a924e7605cfd4c6c25fbce58a9de33101f67727b5adea2 | 1,128 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | be3642f5581a84f836a924e7605cfd4c6c25fbce58a9de33101f67727b5adea2 | 536fdcbf4da7d26cef9e108eaf200c7ceb0a1f7b769887289c7a2c9c4a04cf8a | Estimated effective intrinsic clearance for the sequential oxidative metabolism of diclofenac AG in humans. | From the estimated effective intrinsic clearances for the formation of diclofenac AG from diclofenac (6.8 ml/min/kg) and for the sequential oxidative metabolism of diclofenac AG (5.5 ml/min/kg), it appears that a significant fraction of the intrahepatically formed diclofenac AG may be converted to 4'-hydroxy diclofenac... | 55 |
O=C1CN=C(c2ccccc2)c2cc(Cl)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_msp | 0.63 | ul/min/mg msp | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_msp | hepatic_clearance | intrinsic_clearance | ul_min_mg_msp | null | null | null | human | 0.63 | ul/min/mg msp | false | null | null | null | null | human liver microsomes | human | null | null | null | 18374419 | 0.98 | q4 | hepatic | ce9e18dcf12de20c6e384dd63b7f3090ca481aab125ab7fa72d7a99314f92bc6 | 1,132 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | ce9e18dcf12de20c6e384dd63b7f3090ca481aab125ab7fa72d7a99314f92bc6 | 99cda06c5a0af6a648708bb507aeff2ea09e5271481284af3946a09b270b1c9b | The mean intrinsic clearance (CLint) for nordiazepam across 9 human liver microsome samples was 0.63 µL/min/mg MSP. | 137 | |
O=C1CN=C(c2ccccc2)c2cc(Cl)ccc2N1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_msp | 0.45 | ul/min/mg msp | q4.hepatic_clearance.intrinsic_clearance.ul_min_mg_msp | hepatic_clearance | intrinsic_clearance | ul_min_mg_msp | null | null | null | human | 0.45 | ul/min/mg msp | false | null | null | null | null | human liver microsomes | human | null | null | null | 18374419 | 0.96 | q4 | hepatic | fc12932b8fc671c1f0f3dbbad7ee38eb98164f40a3ee10b3fbd0f907c1b85534 | 1,141 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | fc12932b8fc671c1f0f3dbbad7ee38eb98164f40a3ee10b3fbd0f907c1b85534 | 28a278c25e4082a55c95e222be9161f7773eb910df077af53051bf79ce0a59f1 | Maximum value observed across 9 samples | The maximum intrinsic clearance observed for nordiazepam was 0.45 µL/min/mg MSP. | 137 |
CN(C)CC[C@@H](c1ccc(Cl)cc1)c1ccccn1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 0 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | human | 0 | ul/min/10^6 cells | false | null | null | null | null | human hepatocytes (cryopreserved) | human | null | cyp2d6 | null | 17638540 | 0.97 | q4 | hepatic | 6cb0ce4fd429cf54c2c81a4946042ad8961ca20d3380add1bafcbc1439e4d10b | 1,171 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 6cb0ce4fd429cf54c2c81a4946042ad8961ca20d3380add1bafcbc1439e4d10b | 4b90e0e1215a6c38a27a8eb8242f960bde16a2d34774bda2c56ce62e975648dc | Chlorpheniramine showed a mean intrinsic clearance (CLint) of 0.0 µl/min/10⁶ cells in cryopreserved human hepatocytes. | 74 | |
COc1ccc2c(c1)[C@]13CCCC[C@@H]1[C@H](C2)N(C)CC3 | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 47 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | rat | 47 | ul/min/10^6 cells | false | null | null | null | null | rat hepatocytes | rat | null | null | null | 17638540 | 0.96 | q4 | hepatic | 506b8b732167ff1cb16af081f5a86af6ad8d4832eea3309e153d7b739d574244 | 1,178 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 506b8b732167ff1cb16af081f5a86af6ad8d4832eea3309e153d7b739d574244 | ce0f777646ecf103c2c45a741641717008a769c804cd3ad8cf7ff9359f3343ad | The table of reference compounds measured in rat hepatocytes shows that dextromethorphan has a mean intrinsic clearance (CLint) of 47 µl/min/10⁶ cells. | 89 | |
COc1ccc2c(c1)[C@]13CCCC[C@@H]1[C@H](C2)N(C)CC3 | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | 54 | ml/min/kg | q4.hepatic_clearance.hepatic_clearance.ml_min_kg | hepatic_clearance | hepatic_clearance | ml_min_kg | null | null | null | rat | 54 | ml/min/kg | false | null | null | null | null | rat hepatocytes | rat | null | null | null | 17638540 | 0.96 | q4 | hepatic | 53590b2e063d70d28562da32271b91a686f5e6354ca427114a126cfed50ed37b | 1,179 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 53590b2e063d70d28562da32271b91a686f5e6354ca427114a126cfed50ed37b | c583082f1eb93e59b1c9df51f7b95abd953237e3193b8f977d36918a534595db | The same table reports that dextromethorphan has a calculated hepatic clearance (CLH(calc)) of 54 ml/min/kg. | 89 | |
COc1ccc(CCN(C)CCC[C@@](C#N)(c2ccc(OC)c(OC)c2)C(C)C)cc1OC | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 30 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | rat | 30 | ul/min/10^6 cells | false | null | null | null | null | rat hepatocytes | rat | null | null | null | 17638540 | 0.95 | q4 | hepatic | e15098a6d37b22f16d6962a3f74724d5a11aea3f3fff96f6c8550efeb29d7ff2 | 1,180 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e15098a6d37b22f16d6962a3f74724d5a11aea3f3fff96f6c8550efeb29d7ff2 | 5bb2af1dff1a7f251ab02b98e7d9d8bd1d6bb5584edf1852fee9efffda9eec5e | Verapamil shows a mean intrinsic clearance of 30 µl/min/10⁶ cells in rat hepatocytes. | 89 | |
C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 130 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | human | 130 | ul/min/10^6 cells | false | null | null | null | null | human hepatocytes | human | null | null | null | 27784718 | 0.96 | q4 | hepatic | 84adf68815c2286c30cf513f1d8618c6aa99297156ae19122cd0d9d8cabb8e6a | 1,193 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 84adf68815c2286c30cf513f1d8618c6aa99297156ae19122cd0d9d8cabb8e6a | be6705fce2f5ac2319ee84de7fca364b285f18e72cd8d485a4de0006b57a97ca | Value taken from the CLh int column of the table in paragraph 45. | Table 1 reports a human intrinsic hepatic clearance (CLh int) of 130 µL/min/10^6 cells for ibrutinib (PCI-32765). | 45 |
C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1 | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | 147 | ul/min/10^6 cells | q4.hepatic_clearance.intrinsic_clearance.ul_min_10_6_cells | hepatic_clearance | intrinsic_clearance | ul_min_10_6_cells | null | null | null | rat | 147 | ul/min/10^6 cells | false | null | null | null | null | rat hepatocytes | rat | null | null | null | 27784718 | 0.96 | q4 | hepatic | 557c92951c8940b6e1bf53d1588281857d0248dec4f921285f054b3910af5d64 | 1,194 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 557c92951c8940b6e1bf53d1588281857d0248dec4f921285f054b3910af5d64 | bdd4a9372a8cc932189cbdb32b4c6a6a2a2dc591a6b406f535725d087ec6af52 | Value taken from the CLh int column of the table in paragraph 45. | Table 1 reports a rat intrinsic hepatic clearance (CLh int) of 147 µL/min/10^6 cells for ibrutinib (PCI-32765). | 45 |
COc1ccc2c(c1)[C@]13CCCC[C@@H]1[C@H](C2)N(C)CC3 | q4.hepatic_clearance.intrinsic_clearance.ul_per_min_per_million_cells | 20 | ul per min per million cells | q4.hepatic_clearance.intrinsic_clearance.ul_per_min_per_million_cells | hepatic_clearance | intrinsic_clearance | ul_per_min_per_million_cells | null | null | null | null | 20 | ul per min per million cells | true | 2 | unspecified_variation | null | null | in vitro hepatocyte culture | null | null | cyp2d6/3a4 | null | 35107462 | 0.96 | q4 | hepatic | 936ca789f108eaaed3718d93a24494b56a20fb6ab652c544f1fefbd8e24a4f90 | 1,197 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 936ca789f108eaaed3718d93a24494b56a20fb6ab652c544f1fefbd8e24a4f90 | 05de78e490ce522aa599bfaf49a9d598ae10589fe4daddd3e3dbc2ef2e6b67f1 | Footnote e in the table. | For dextromethorphan the table reports an in vitro intrinsic clearance (CLint,u) of 20 ± 2 µL per min per million cells. | 20 |
CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccc(F)cc3)[nH]c3ccc(CN4CCC(C(C)(C)O)CC4)cc32)CC1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg | 3.8 | l/h*kg | q4.hepatic_clearance.hepatic_clearance.l_h_kg | hepatic_clearance | hepatic_clearance | l_h_kg | null | null | null | mouse | 3.8 | l/h*kg | false | null | null | null | null | in vitro kinetic model (hydrolysis and nadph‐dependent pathways) | mouse | null | null | null | 23118327 | 0.98 | q4 | hepatic | c56bfb30e56654fb71e75b7229df9e7830a3d29842e37cf15aee18fe75f9e128 | 1,227 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | c56bfb30e56654fb71e75b7229df9e7830a3d29842e37cf15aee18fe75f9e128 | 0a2262cf91fb4d4c8a65214148013681c2122865ece9de3a070c151ac04b2661 | Prediction incorporates contributions from hydrolysis and NADPH‑dependent metabolism. | Predicted hepatic clearance for compound 1 was 3.8 L/h·kg, based on kinetic data from both hydrolytic and NADPH‑dependent metabolism pathways. | 1 |
CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3cc(F)cc(F)c3)[nH]c3ccc(CN4CCC(C(C)(C)O)CC4)cc32)CC1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg | 3 | l/h*kg | q4.hepatic_clearance.hepatic_clearance.l_h_kg | hepatic_clearance | hepatic_clearance | l_h_kg | null | null | null | mouse | 3 | l/h*kg | false | null | null | null | null | in vitro kinetic model (hydrolysis and nadph‐dependent pathways) | mouse | null | null | null | 23118327 | 0.98 | q4 | hepatic | e5bc2edb70abdbe70475223ba6e1e38e2080b12284051d603e01009a4a58a4bb | 1,228 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | e5bc2edb70abdbe70475223ba6e1e38e2080b12284051d603e01009a4a58a4bb | 0d8ce7a824c6e6528a7cfd03b26c20d2afaec64f5769cfcd549021b32e41de6b | Prediction incorporates contributions from hydrolysis and NADPH‑dependent metabolism. | Predicted hepatic clearance for compound 2 was 3.0 L/h·kg, derived from the same in vitro kinetic approach. | 1 |
CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3cc(F)cc(Cl)c3)[nH]c3ccc(CN4CCC(C(C)(C)O)CC4)cc32)CC1 | q4.hepatic_clearance.hepatic_clearance.l_h_kg | 1.6 | l/h*kg | q4.hepatic_clearance.hepatic_clearance.l_h_kg | hepatic_clearance | hepatic_clearance | l_h_kg | null | null | null | mouse | 1.6 | l/h*kg | false | null | null | null | null | in vitro kinetic model (hydrolysis and nadph‐dependent pathways) | mouse | null | null | null | 23118327 | 0.98 | q4 | hepatic | 1a39303d4e334d66141fdfa50d43fbc94ec797083a0f5f91b3e07ae886865739 | 1,229 | e78b8190ddf01bfb2f6f415931557ce6f610859ab5f9af481207a2fadb075d5e | 1a39303d4e334d66141fdfa50d43fbc94ec797083a0f5f91b3e07ae886865739 | 7e193e045b29aebb57748e9e6c8bdfb2da4e73575191ab9a16f64c56764c083c | Prediction incorporates contributions from hydrolysis and NADPH‑dependent metabolism. | Predicted hepatic clearance for compound 3 was 1.6 L/h·kg, based on kinetic data from hydrolysis and NADPH‑dependent pathways. | 1 |
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