Transplacental transfer of oseltamivir carboxylate

Abstract

Objectives: Determine the bidirectional transfer of oseltamivir carboxylate (OC) across term human placenta and its distribution between the tissue, maternal and fetal circuits. Methods: The technique of dual perfusion of placental lobule (DPPL) in its recirculating mode was utilized to determine the transfer of the drug. OC (350 ng/mL) was co-perfused with its [³H]-isotope and the marker compound antipyrine (AP, 20 µg/mL) together with its [¹⁴C]-isotope. The concentrations of OC and any of its metabolite(s) formed during perfusion were determined in the tissue, maternal and fetal circuits by liquid scintillation spectrometry following their separation by High Performance Liquid Chromatography (HPLC). Results: The distribution of OC following its perfusion in the Maternal-to-Fetal direction for 4 h was as follows: 21 ± 4% of the drug was transferred to the fetal circuit, 13 ± 5% was retained by the perfused lobule, and 66 ± 4% remained in the maternal circuit. The normalized transfer of OC to that of AP (Clearance index) in the maternal-to-fetal direction was (0.47 ± 0.11) and was not different from its transfer from the fetal-to-maternal direction (0.47 ± 0.06) suggesting that involvement of placental efflux transporters is unlikely. Conclusions: OC crosses human placenta. As the transfer rate of OC is 47% of the freely diffusible AP, it is likely that fetus could be exposed to OC during pregnancy.

Keywords::

• H1N1 influenza virus
• oseltamivir carboxylate
• pregnancy
• tamiflu
• transplacental transfer

Acknowledgement

The authors sincerely appreciate the support of the physicians and nurses of the Labor & Delivery Ward of the John Sealy Hospital, the teaching hospital at UTMB, Galveston, Texas, the Perinatal Research Division, and the Publication, Grant, & Media Support division of the Department of Obstetrics & Gynecology. The authors greatly appreciate F. Hoffmann-La Roche Ltd (Pharma Research, Basel, Switzerland) for their generous gift of oseltamivir carboxylate. This work was supported by a U10-HD 047891 (Obstetrics-Fetal Pharmacology Research Units).

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this manuscript.