Bioequivalence and Bioavailability Forum

Dear All
In an open-label, randomized, four period, 2 x two-way crossover study, we measured the relative bioavailability of tablets containing prasugrel free base compared to prasugrel hydrochloride (EfientTM) both in the presence and in the absence of the proton pump inhibitor lansoprazole was investigated. For this, a respective analytical method for the determination of prasugrel active metabolite was successfully developed and validated. RESULTS: In the absence of lansoprazole, the extent of absorption (AUC) of prasugrel free base is about 8-9% lower, while the rate of absorption (Cmax) after administration of prasugrel free base is about 20% lower when compared to prasugrel hydrochloride. When lansoprazole is used to raise the pH level in the upper gastro-intestinal tract, the relative bioavailability is decreased by about 25% after administration of prasugrel hydrochloride and by about 41% after administration of prasugrel free base. In addition, the peak plasma levels are decreased by about 52% and 72%, respectively (geom. means). CONCLUSION: The relative bioavailability of the prasugrel free base compared to prasugrel hydrochloride, both in the presence and in the absence of the proton pump inhibitor lansoprazole, differs so much that most probably it will not be possible to develop a generic formulation containing prasugrel free base that would be bioequivalent in all aspects to EfientTM.
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Dan