A Strategy to Refine the Phenotyping Approach and Its Implementation to Predict Drug Clearance: A Physiologically Based Pharmacokinetic Simulation Study.

ABSTRACT: The phenotyping approach to predict drug metabolism activity is often hampered by a lack of correlation between the probe and the drug of interest. In this article, we present a strategy to refine the phenotyping approach based on a physiologically based pharmacokinetic simulation (implemented in Simcyp Simulator version 17) using previously published models. The apparent clearance (CL/F) of erlotinib was better predicted by the sum of caffeine and i.v. midazolam CL/F (r²  = 0.60) compared to that of either probe drug alone. The clearance of atorvastatin and repaglinide had a strong correlation (r²  = 0.70 and 0.63, respectively) with that of pitavastatin (a SLCO1B1 probe). Use of multiple probes for drugs that are predominantly metabolized by more than one cytochrome

SUBMITTER: Adiwidjaja J 

PROVIDER: S-EPMC6310868 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature