Effects of the Proton Pump Inhibitor Lansoprazole on the Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel
| Autor: | David S. Small, Ying G. Li, Kenneth J. Winters, Nagy A. Farid, Daniel E. Salazar, Govinda Weerakkody, Christopher D. Payne, John T. Brandt |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Ticlopidine Prasugrel Adolescent Platelet Aggregation Thienopyridine medicine.drug_class Metabolite Lansoprazole Biological Availability Proton-pump inhibitor Thiophenes Pharmacology 2-Pyridinylmethylsulfinylbenzimidazoles Piperazines chemistry.chemical_compound Pharmacokinetics medicine Humans Drug Interactions Pharmacology (medical) cardiovascular diseases Active metabolite Aged Cross-Over Studies business.industry Proton Pump Inhibitors Middle Aged Clopidogrel Adenosine Diphosphate chemistry Area Under Curve Female business Prasugrel Hydrochloride Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 48:475-484 |
| ISSN: | 0091-2700 |
| Popis: | Prasugrel and clopidogrel, thienopyridine prodrugs, are each metabolized to an active metabolite that inhibits the platelet P2Y(12) ADP receptor. In this open-label, 4-period crossover study, the effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel were assessed in healthy subjects given single doses of prasugrel 60 mg and clopidogrel 300 mg with and without concurrent lansoprazole 30 mg qd. C(max) and AUC(0-tlast) of prasugrel's active metabolite, R-138727, and clopidogrel's inactive carboxylic acid metabolite, SR26334, were assessed. Inhibition of platelet aggregation (IPA) was measured by turbidimetric aggregometry 4 to 24 hours after each treatment. Lansoprazole (1) decreased R-138727 AUC(0-tlast) and C(max) by 13% and 29%, respectively, but did not affect IPA after the prasugrel dose, and (2) did not affect SR62334 exposure but tended to lower IPA after a clopidogrel dose. A retrospective tertile analysis showed in subjects with high IPA after a clopidogrel dose alone that lansoprazole decreased IPA, whereas IPA was unaffected in these same subjects after a prasugrel dose. The overall data suggest that a prasugrel dose adjustment is not likely warranted in an individual taking prasugrel with a proton pump inhibitor such as lansoprazole. |
| Databáze: | OpenAIRE |
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