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Methods: PBPK modelling and simulation was employed using Simcyp Simulator (v15.1). Virtual populations were generated assuming inter-correlations between hepatic CYP3A4-CYP2C8 abundances derived from observed values in 24 human livers [1]. A repaglinide PBPK model was used to predict pharmacokinetic parameters in presence and absence of gemfibrozil, an inhibitor of CYP2C8, in virtual populations, and the results were compared with a clinical DDI study [2].

nihon yakuri gakkai nenkai yoshishu

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