The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model

UNLABELLED Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete. OBJECTIVE To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model. STUDY DESIGN Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20-30 fold, and 600-800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the (14)C antipyrine reference method. RESULTS OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of 0.13 +/- 0.08, suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations. CONCLUSIONS Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.