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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Transplacental Transfer and Metabolism of Buprenorphine

Tatiana Nanovskaya, Sujal Deshmukh, Monica Brooks and Mahmoud S. Ahmed
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 26-33; DOI: https://doi.org/10.1124/jpet.300.1.26
Tatiana Nanovskaya
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Sujal Deshmukh
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Monica Brooks
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Mahmoud S. Ahmed
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Abstract

Information on the direct and indirect effects of buprenorphine (BUP) on the fetus is essential for determining its potential for treatment of the pregnant opiate addict. The goal of this investigation is to determine the transplacental transfer of BUP to the fetal circulation, its metabolism, and effects on the tissue. The technique of dual perfusion of placental lobule is used. The range of BUP concentrations investigated included its peak plasma levels (10 ng/ml) in patients under treatment. A biphasic decline in concentration of the drug in the maternal circulation was observed, initially rapid then slow. During the initial (60 min), the tissue sequestered most of BUP resulting in a low (<10%) transplacental transfer of the drug to the fetal circulation. The concentration ratios of the drug in tissue/maternal and tissue/fetal were 13 ± 6.5 and 27.4 ± 0.4. The drug sequestered did not have any adverse effects on placental tissue viability and functional parameters. Less than 5% of the perfused BUP was metabolized to norbuprenorphine during the 4 h of perfusion and the metabolite was distributed between the tissue, maternal, and fetal circulations. Taken together, these data suggest that the therapeutic levels of BUP in the maternal circulation may have no indirect effects (via the placenta) on the fetus. The observed low transplacental transfer of BUP to the fetal circuit may explain the moderate/absence of neonatal withdrawal in the limited number of reports on mothers treated with the drug during pregnancy.

Footnotes

  • This work was supported in part by grant from the National Institute on Drug Abuse (DA13431) to M.S.A.

  • Abbreviations

    BUP
    buprenorphine
    CYP
    cytochrome P450
    hCG
    human chorionic gonadotropin
    AP
    antipyrine
    AUC
    area under the concentration-time curve
    norBUP
    norbuprenorphine
    HPLC
    high-performance liquid chromatography
    • Received July 6, 2001.
    • Accepted September 12, 2001.
    • The American Society for Pharmacology and Experimental Therapeutics
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    Journal of Pharmacology and Experimental Therapeutics: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
    Vol. 300, Issue 1
    1 Jan 2002
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    Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

    Transplacental Transfer and Metabolism of Buprenorphine

    Tatiana Nanovskaya, Sujal Deshmukh, Monica Brooks and Mahmoud S. Ahmed
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 26-33; DOI: https://doi.org/10.1124/jpet.300.1.26

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    Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

    Transplacental Transfer and Metabolism of Buprenorphine

    Tatiana Nanovskaya, Sujal Deshmukh, Monica Brooks and Mahmoud S. Ahmed
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 26-33; DOI: https://doi.org/10.1124/jpet.300.1.26
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