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


METHODS
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.
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center Dallas, TX 75390-9032, USA. kevin.worley@mac.com
Kevin C
KC
Worley
Scott W
SW
Roberts
Roger E
RE
Bawdon
D000983:Antipyrine / Q000378:metabolism; D000998:Antiviral Agents / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D053139:Oseltamivir / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D000998:Antiviral Agents; D053139:Oseltamivir; D000983:Antipyrine