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dc.contributor.authorStringer, R.
dc.contributor.authorNicklin, P.L.
dc.contributor.authorHouston, J.B.
dc.identifier.citationStringer , 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 .
dc.identifier.otherPURE: 2463904
dc.identifier.otherPURE UUID: 3d6432f0-78b3-45f9-b6cf-53fa00af98d9
dc.identifier.otherScopus: 53849115780
dc.description.abstractA 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.titleReliability of human cryopreserved hepatocytes and liver microsomes as in vitro systems to predict metabolic clearanceen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Pharmacy
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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