Transplacental transfer of oseltamivir carboxylate

Tatiana Nanovskaya, Svetlana Patrikeeva, Ying Zhan, Gary Hankins, Mahmoud Ahmed

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 (350ng/mL) was co-perfused with its [ 3H]-isotope and the marker compound antipyrine (AP, 20 g/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 4h 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.

Original languageEnglish (US)
Pages (from-to)2312-2315
Number of pages4
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume25
Issue number11
DOIs
StatePublished - Nov 2012

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Mothers
Fetus
Perfusion
Isotopes
Placenta
Antipyrine
oseltamivir carboxylate
Tissue Distribution
Pharmaceutical Preparations
Spectrum Analysis
High Pressure Liquid Chromatography
Pregnancy
Direction compound

Keywords

  • H1N1 influenza virus
  • Oseltamivir carboxylate
  • Pregnancy
  • Tamiflu
  • Transplacental transfer

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Transplacental transfer of oseltamivir carboxylate. / Nanovskaya, Tatiana; Patrikeeva, Svetlana; Zhan, Ying; Hankins, Gary; Ahmed, Mahmoud.

In: Journal of Maternal-Fetal and Neonatal Medicine, Vol. 25, No. 11, 11.2012, p. 2312-2315.

Research output: Contribution to journalArticle

Nanovskaya, Tatiana ; Patrikeeva, Svetlana ; Zhan, Ying ; Hankins, Gary ; Ahmed, Mahmoud. / Transplacental transfer of oseltamivir carboxylate. In: Journal of Maternal-Fetal and Neonatal Medicine. 2012 ; Vol. 25, No. 11. pp. 2312-2315.
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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 (350ng/mL) was co-perfused with its [ 3H]-isotope and the marker compound antipyrine (AP, 20 g/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 4h 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.",
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AB - 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 (350ng/mL) was co-perfused with its [ 3H]-isotope and the marker compound antipyrine (AP, 20 g/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 4h 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.

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