Interlaboratory Variability in Human Hepatocyte Intrinsic Clearance Values and Trends with Physicochemical Properties.

ABSTRACT:

Purpose

To examine the interlaboratory variability in CL_int values generated with human hepatocytes and determine trends in variability and clearance prediction accuracy using physicochemical and pharmacokinetic parameters.

Methods

Data for 50 compounds from 14 papers were compiled with physicochemical and pharmacokinetic parameter values taken from various sources.

Results

Coefficients of variation were as high as 99.8% for individual compounds and variation was not dependent on the number of prediction values included in the analysis. When examining median values, it appeared that compounds with a lower number of rotatable bonds had more variability. When examining prediction uniformity, those compounds with uniform in vivo underpredictions had higher CL<

SUBMITTER: Bowman CM 

PROVIDER: S-EPMC7191673 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature