Physiologically based pharmacokinetic modeling for sequential metabolism: effect of CYP2C19 genetic polymorphism on clopidogrel and clopidogrel active metabolite pharmacokinetics.

Abstract excerpt

Clopidogrel is a prodrug that needs to be converted to its active metabolite (clopi-H4) in two sequential cytochrome P450 (P450)-dependent steps. In the present study, a dynamic physiologically based pharmacokinetic (PBPK) model was developed in Simcyp for clopidogrel and clopi-H4 using a specific sequential metabolite module in four populations with phenotypically different CYP2C19 activity (poor, intermediate,...

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