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Transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate using the ex vivo human placenta perfusion model in Chinese Hans population

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  • Transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate using the ex vivo human placenta perfusion model in Chinese Hans population

    J Matern Fetal Neonatal Med. 2016 Jul 18:1-10. [Epub ahead of print]
    Transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate using the ex vivo human placenta perfusion model in Chinese Hans population.

    Huang H1, Wang J1, Li Q1, Duan J2, Yao Q1, Zheng Q1, Wang J1, Wu D1, Zhou Q1, Tian Y3, Zhang J1.
    Author information

    Abstract

    OBJECTIVE:

    The objective of the study was to determinetransplacental of oseltamivir phosphate and its active metabolite oseltamivir carboxylate using the ex vivo human placental perfusion model in Chinese Hans population.
    STUDY DESIGN:

    Perfusion studies were performed on twenty placentas from healthy term pregnancies. Concentrations typical for an 75mg, twice-daily oral dose were tested(oseltamivir phosphate 65.2 ng/ml and oseltamivir carboxylate 348 ng/ml), along with the positive control antipyrine 0.1 mg/ml. Each perfusion experiment was conducted for 180 minutes while samples were taken from both maternal and fetal compartments. Concentrations of oseltamivir phosphate and its metabolite oseltamivir carboxylate 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 hours of perfusion, the fetal transfer ratesof oseltamivir phosphate,and its metabolite oseltamivir carboxylate 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 oseltamivir phosphate and its metabolite oseltamivir carboxylate 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 oseltamivir phosphate.


    KEYWORDS:

    ex vivo human placenta perfusion model; influenza; oseltamivir phosphate; pregnancy; transplacental transfer

    PMID: 27426925 DOI: 10.1080/14767058.2016.1211634
    [PubMed - as supplied by publisher]
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