Oseltamivir oral suspension and capsules are bioequivalent for the active metabolite in healthy adult volunteers

摘要

Aims: The objective of this study was to assess the relative bioavailability of oseltamivir carboxylate (active metabolite) following oral administration of the market suspension, the clinical trial suspension and the market capsule formulations of oseltamivir (prodrug) in healthy subjects. Methods: In this single-center, open-label, three-period crossover study, 24 healthy adult volunteers were randomized to receive one dose (150 mg oseltamivir) of each of the three formulations (market suspension, clinical trial suspension, market capsule formulation), with a 7-day washout period between each administration. Blood samples, collected for up to 48 h post-dosing, were analyzed for plasma oseltamivir and oseltamivir carboxylate. Adverse events were monitored. Results: Pharmacokinetic parameters for oseltamivir and oseltamivir carboxylate were similar for the three formulations. Bioequivalence for oseltamivir carboxylate was demonstrated between the market capsule and the two suspensions: 90% confidence intervals for the log-transformed C_(max), AUC_(last) and AUC_(inf) ratios fell within the 80 - 125% criteria. Similarly, the two suspensions were also demonstrated as bio-equivalent for oseltamivir carboxylate. Oseltamivir was well tolerated. The majority of adverse events observed were mild in intensity, with the most common being nausea and headache. Conclusions: This study demonstrates that the market suspension, the clinical trial suspension and the market capsule formulations of oseltamivir are bioequivalent for the active metabolite, oseltamivir carboxylate. Based on this finding, the market suspension may be used to achieve comparable exposure in patients unable to take capsules.