dc.contributor.author | Stringer, R. | |
dc.contributor.author | Nicklin, P.L. | |
dc.contributor.author | Houston, J.B. | |
dc.date.accessioned | 2013-10-16T20:30:02Z | |
dc.date.available | 2013-10-16T20:30:02Z | |
dc.date.issued | 2008-10-01 | |
dc.identifier.citation | Stringer , R , Nicklin , P L & Houston , J B 2008 , ' Reliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearance ' , Xenobiotica , vol. 38 , no. 10 , pp. 1313-1329 . https://doi.org/10.1080/00498250802446286 | |
dc.identifier.issn | 0049-8254 | |
dc.identifier.other | PURE: 2463904 | |
dc.identifier.other | PURE UUID: 3d6432f0-78b3-45f9-b6cf-53fa00af98d9 | |
dc.identifier.other | Scopus: 53849115780 | |
dc.identifier.uri | http://hdl.handle.net/2299/11791 | |
dc.description.abstract | A total of 110 drugs, selected to cover a range of physicochemical and pharmacokinetic properties, were used to explore standard approaches to the prediction of in vivo metabolic clearance using drug-depletion profiles from human liver microsomes (HLMs) and cyropreserved hepatocytes. A total of 41 drugs (37% of the compounds tested) showed measurable depletion rates using HLMs (depletion by 20% or more over the time course). The most reliable correlations in terms of bias (average fold error (AFE) = 2.32) and precision (root mean square error (RMSE) = 3501) were observed by comparing in vivo intrinsic clearance (CLint), calculated using the parallel-tube model and incorporating the fraction unbound in blood, with in vitro CLint adjusted for microsomal binding. For these reference drugs, 29% of predictions were within two-fold of the observed values and 66% were within five-fold. Compared with HLMs, clearance predictions with cryopreserved hepatocytes (57 drugs) were of similar precision (RMSE = 3608) but showed more bias (AFE = 5.21) with 18% of predictions within two-fold of the observed values and 46% within five-fold. However, with a broad complement of drug-metabolizing enzymes, hepatocytes catalysed measurable CLint values for a greater proportion (52%) of the reference compounds and were particularly proficient at defining metabolic rates for drugs with predominantly phase 2 metabolic routes. | en |
dc.format.extent | 17 | |
dc.language.iso | eng | |
dc.relation.ispartof | Xenobiotica | |
dc.title | Reliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearance | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Department of Pharmacy | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | https://doi.org/10.1080/00498250802446286 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |