Takeda Pharmaceuticals North America, Inc. (Takeda) announced the presentation of new study results, which evaluated the potential inhibitory effects of certain proton pump inhibitors (PPIs) on Plavix (clopidogrel bisulfate). The results showed that in healthy subjects, clopidogrel's active metabolite and inhibition of platelet function were reduced less by the co-administration of clopidogrel with dexlansoprazole or lansoprazole, rather than esomeprazole. The randomized, open-label, two-period, crossover study was designed to assess the effects of selected PPIs, a class of drugs used to treat gastroesophageal reflux disease, on the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel. Clopidogrel is a platelet-inhibiting drug that is indicated for the reduction of atherothrombotic events in patients with acute coronary syndromes, recent myocardial infarction, recent stroke or established peripheral arterial disease. The results were presented at the American College of Cardiology (ACC) 2011 60th Annual Scientific Session in New Orleans.
Studies have shown that PPIs may inhibit a liver enzyme (CYP2C19) important for the metabolism of clopidogrel. With CYP2C19 inhibition, clopidogrel may have reduced antiplatelet effects, potentially reducing its effectiveness. Because PPIs differ in their degree of inhibition of CYP2C19, using omeprazole as a positive control, this study evaluated the effect of several PPIs (dexlansoprazole, lansoprazole and esomeprazole) on the steady-state PK and PD of clopidogrel in healthy subjects.
"We conducted this study to look at the effect of select PPIs on Plavix and add to the growing body of evidence on the potential interaction between these drugs," said lead investigator Alan D. Michelson, M.D., Professor of Pediatrics at Harvard Medical School and Director of the Center for Platelet Research Studies at Children's Hospital Boston. "We found that in healthy subjects the co-administration of Plavix with dexlansoprazole or lansoprazole reduced the antiplatelet effect of Plavix less than the co-administration of Plavix with esomeprazole."