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Abstract
Objective: The objective of the study was to determine transplacental of oseltamivir phosphate (OP) and its active metabolite oseltamivir carboxylate (OC) using the ex vivo human placental perfusion model in Chinese Hans population.
Study design: Perfusion studies were performed on 20 placentas from healthy term pregnancies. Concentrations typical for 75 mg, twice-daily oral dose were tested (OP 65.2 ng/ml and OC 348 ng/ml), along with the positive control antipyrine 0.1 mg/ml. Each perfusion experiment was conducted for 180 min while samples were taken from both maternal and fetal compartments. Concentrations of OP and its metabolite OC were determined by ultrafast-performance liquid chromatography/tandem mass spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments.
Results: Following 3 h of perfusion, the fetal transfer rates of OP and its metabolite OC were 12.39%±3.26%, 10.17%±2.03%, respectively. The clearance indexes of OP and OC were 0.36 ± 0.11 and 0.29 ± 0.06, respectively.
Conclusion: These data suggest that OP and its metabolite OC pass through the healthy term placenta at a small amount according to the ex vivo human placental perfusion model, fetal exposure must be considered when treating pregnant women with OP.
Declaration of interest
The authors report no conflicts of interest.
For multiple agency grants, this work was supported by the National Natural Science Foundation of China (81360108); and the Union Specific Foundation of Yunnan Province Technology Department and Kunming Medical University (2013FB139); and the Health & technology projects of Yunnan Province (2014NS189).