Evaluating the use of Cryopreserved Hepatocytes for the Prediction of In Vivo Hepatic Clearance

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Title:	Evaluating the use of Cryopreserved Hepatocytes for the Prediction of In Vivo Hepatic Clearance
Author:	Eng, Heather S.
Description:	This study examines the clearance of five therapeutic drugs, carbamazepine, phenytoin, procainamide, quinidine, and theophylline, in an in vitro hepatocyte suspension. Parent drug concentration was measured via fluorescence polarization immunoassay or high performance liquid chromatography as a function of time. Parent drug disappearance data were used to calculate linear one-hour disappearance (parent drug activity) and intrinsic in vitro clearance rates. The in vitro clearance value was scaled to a prediction of human in vivo hepatic clearance using the well-stirred model. No correlation between parent drug activity or predicted in vivo hepatic clearance and reported donor characterization was observed. Observed intrinsic in vitro clearance rates were unsuccessful at accurately predicting in vivo hepatic clearance. Therefore, these results are inconclusive regarding the potential use of cryopreserved hepatocytes for the preclinical estimation of human in vivo hepatic clearance.
Permanent Link:	http://rave.ohiolink.edu/etdc/view?acc_num=toledo1091638312 http://hdl.handle.net/2374.OX/19391
Date:	2004

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