13C]Pantoprazole breath test as a predictor of the anti-platelet function of clopidogrel

Abstract

Clopidogrel, a platelet inhibitor, is metabolized by cytochrome P450 2C19 (CYP2C19) to its active metabolite and, consequently, its anti-platelet efficacy is influenced by CYP2C19 activity. The aim of this study was to determine whether the [(13)C]pantoprazole breath test, a recently developed tool used to measure CYP2C19 activity, can predict the anti-platelet efficacy of clopidogrel. Seventy healthy volunteers with different CYP2C19 genotypes received 100 mg of [(13)C]pantoprazole. Breath samples were collected at 10-min intervals for 60 min, and changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) from the baseline level were measured and expressed as a delta-over-baseline (DOB) ratio (per thousand). After a washout period of > 2 weeks, the subjects underwent a platelet aggregation test before and after dosing with 75 mg of clopidogrel for 7 days. The percentage inhibition of platelet aggregation (IPA, %) was then calculated. There was a statistically significant correlation between the area under the curve (AUC)(20-60 min) of the DOB and IPA at 4 h attained by clopidogrel. The mean AUC(20-60 min) of the DOB of the "low-responder" (IPA < 20%) group was significantly lower than that of the responder group (IPA > or = 20%). The results of our preliminary study suggest that the [(13)C]pantoprazole breath test can predict the anti-platelet efficacy of clopidogrel.