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 [(3)H]-isotope and the marker compound antipyrine (AP, 20 µg/mL) together with its [(14)C]-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.
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 [(3)H]-isotope and the marker compound antipyrine (AP, 20 µg/mL) together with its [(14)C]-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.
Authors: Timothy M Uyeki; Henry H Bernstein; John S Bradley; Janet A Englund; Thomas M File; Alicia M Fry; Stefan Gravenstein; Frederick G Hayden; Scott A Harper; Jon Mark Hirshon; Michael G Ison; B Lynn Johnston; Shandra L Knight; Allison McGeer; Laura E Riley; Cameron R Wolfe; Paul E Alexander; Andrew T Pavia Journal: Clin Infect Dis Date: 2019-03-05 Impact factor: 9.079
Authors: Tatiana N Nanovskaya; Svetlana L Patrikeeva; Jonathan Paul; Maged M Costantine; Gary D V Hankins; Mahmoud S Ahmed Journal: Am J Obstet Gynecol Date: 2013-10 Impact factor: 8.661
Authors: Sophie Graner; Tobias Svensson; Anna-Belle Beau; Christine Damase-Michel; Anders Engeland; Kari Furu; Anders Hviid; Siri Eldevik Håberg; Ditte Mølgaard-Nielsen; Björn Pasternak; Helle Kieler Journal: BMJ Date: 2017-02-28