Chemical analysis and transplacental transfer of oseltamivir and oseltamivir carboxylic acid in pregnant rats

PloS One
Chia-Chun LinTung-Hu Tsai

Abstract

In view of the limited information on the pharmacokinetics of oseltamivir (OSE) during pregnancy, this study aims to evaluate the placental transportation of OSE and its active metabolite oseltamivir carboxylic acid (OCA) in rats. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) system coupled to an in vivo transplacental model has been developed to determine OSE and OCA in the placenta, amniotic fluids and fetus of 13-day pregnant Sprague-Dawley rats. Concentrations of OSE and OCA in plasma, amniotic fluids, placenta, and fetus were measured by the validated LC-MS/MS after OSE administration (10 mg/kg, i.v.). The pharmacokinetic data of both analytes were examined by non-compartmental modeling. The area under the concentration-time curve (AUC) of OCA in maternal plasma was found to be 3.6 times larger than that of OSE. The AUCs of OCA in both amniotic fluid and fetus were significantly decreased, in comparison with that in maternal plasma (reduced by 76.7 and 98.1%, respectively). We found that both OSE and OCA can penetrate the placenta, amniotic fluids and fetus in rats during pregnancy; however, the penetration of OCA was much lower than that of OSE. The mother-to-fetus transfer ratio was defined as AUC...Continue Reading

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Citations

Jul 30, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ya-Ning Chang, Tung-Hu Tsai
Jul 1, 2021·Open Forum Infectious Diseases·Eric J ChowTimothy M Uyeki

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Methods Mentioned

BETA
enzymatic assay

Software Mentioned

MassLynx
WinNonlin

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