The metabolism and transplacental transfer of oseltamivir in the ex vivo human model

Infectious Diseases in Obstetrics and Gynecology
Kevin C WorleyRoger E Bawdon

Abstract

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model. 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. 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. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.

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Methods Mentioned

BETA
NMR

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