Implications of inter ‐correlation between hepatic CYP3A4‐CYP2C8 enzymes for the evaluation of drug‐drug interactions: a case study with repaglinide

ConclusionsThe present study demonstrates via a systematic investigation that population‐based PBPK modelling incorporating inter‐correlation led to more consistent estimation of extreme values with those observed in inter‐individual variabilities of clearance and DDI. As the inter‐correlations more realistically reflect enzyme abundances, virtual population studies involving PBPK and DDI should avoid using Monte Carlo assignment of enzyme abundance.

Source: British Journal of Clinical Pharmacology - January 30, 2018 Category: Drugs & Pharmacology Authors: Kosuke Doki, Adam S. Darwich, Brahim Achour, Aleksi Tornio, Janne T. Backman, Amin Rostami ‐Hodjegan Tags: DRUG INTERACTIONS Source Type: research