The purposes were to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil.Thus, we conducted an open-label, two-phase cross-over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and 9 CYP2C19*17/*17). In phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and the platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix®). In phase B, the pharmacokinetics of proguanil and its metabolites, cycloguanil and 4-chlorphenylbiguanide, were determined in 29 of the 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone®.Statistically significant correlations between the area under the time-concentration curve (AUC0-∞) of CAMD on the one hand and both the absolute ADP-induced P2Y12-activated platelet aggregation (PRU) (r=-0.60, p=0.0007) and the percent inhibition of aggregation (r=0.59, p=0.0009) on the other hand were found. Besides, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had statistically significantly higher percent inhibition of platelet aggregation compared to the group of CYP2C19*1/*1 subjects (geometric mean of 84%, 73% and 63%, respectively, p=0.014). Neither the PRU, the exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4-chlorphenylbiguanide showed any statistically significant differences between the genotype groups.In conclusion, carriers of CYP2C19*17 display higher percent inhibition of platelet aggregation but do not have significantly lower absolute P2Y12-activated platelet aggregation or higher exposure of the active metabolite after a single oral administration of 600 mg clopidogrel.This article is protected by copyright. All rights reserved.