Effect of concurrent omeprazole-clopidogrel administration on platelet function and clopidogrel metabolism in healthy cats

Christina Plante

The importance of drug interactions and individual responses to drugs is becoming a very active part of research in veterinary medicine. Cats may have comorbidities requiring a plethora of medications increasing the likelihood of such drug interactions. Clopidogrel is a prodrug that has a high dependency on the hepatic cytochrome P450 system. Omeprazole can inhibit the cytochrome P450 system and consequently alter the efficacy of clopidogrel. The objective of this study was to determine whether the concurrent use of omeprazole with clopidogrel interferes with the metabolism and antiplatelet effects of clopidogrel in healthy cats. In this two-sequence, two-period, two-treatment randomized crossover study, 10 healthy cats were randomly assigned to receive clopidogrel only (18.75 mg per os q24h) or clopidogrel with omeprazole (1mg/kg per os q12h) for 10 days, followed by a 2-week washout period, and then the opposite treatment for another 10 days. Cats were recruited through a volunteer, informed consent basis. Blood was collected via jugular venipuncture on day 0, 5, and 10. Clopidogrel metabolism was evaluated through quantification of clopidogrel parent, clopidogrel carboxylic acid, and clopidogrel active metabolite using high performance liquid chromatography-tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate analyzer, and Platelet Function Analyzer-100 (PFA-100). Multiplate analyzer and PFA-100 were not able to detect any differences in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < 0.001) in platelet function when comparing day 0 to day 5 and day 0 to day 10 in both treatment groups, but it did not reveal any statistical differences between treatment groups. Clopidogrel active metabolite and clopidogrel carboxylic acid were significantly lower on day 10 (P < 0.02 and P < 0.001 respectively) in cats receiving clopidogrel and omeprazole versus clopidogrel only. In conclusion, the concurrent use of omeprazole with clopidogrel was associated with a change in pharmacokinetics on day 10, but a difference in pharmacodynamics between the two treatment groups could not be detected with the platelet function tests used in this study. The short-term use of clopidogrel and omeprazole does not seem to alter platelet function significantly.

Effect of concurrent omeprazole-clopidogrel administration on platelet function and clopidogrel metabolism in healthy cats

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