Placental transfer of diphenhydramine in chronically instrumented pregnant sheep

Authors

  • S. D. Yoo,

    1. Faculty of Pharmaceutical Sciences, Faculty of Medicine and Shaughnessy Research Center, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5
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  • J. E. Axelson,

    Corresponding author
    1. Faculty of Pharmaceutical Sciences, Faculty of Medicine and Shaughnessy Research Center, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5
    • Faculty of Pharmaceutical Sciences, Faculty of Medicine and Shaughnessy Research Center, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5
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  • S. M. Taylor,

    1. Department of Obstetrics and Gynaecology, Faculty of Medicine and Shaughnessy Research Center, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5
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  • D. W. Rurak

    1. Department of Obstetrics and Gynaecology, Faculty of Medicine and Shaughnessy Research Center, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1W5
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Abstract

To study the placental transfer and pharmacokinetics of the H1 receptor blocker, diphenhydramine [2-(diphenylmethoxy)-N,N-dimethylethylamine], 100 mg of the drug was administered to four pregnant sheep (122–129 d gestation) by intravenous injection through catheters chronically implanted in the ewe and fetus. Rapid placental transfer occurred, with peak fetal plasma concentrations occurring within 5 min after injection. The fetal-maternal ratio of the area under the plasma concentration versus time curves averaged 0.85, indicating significant fetal exposure to the drug. The average apparent terminal elimination half-life in the ewe (52 min) was not significantly different from that obtained in the fetus (46 min). The maternal total body clearance was 3.6 L.h−1.kg−1, and the volume of distribution at steady state was 3.2 L/kg. In summary, this study demonstrates rapid and extensive placental transfer of diphenhydramine after maternal drug administration. Since placental permeability to lipid-soluble compounds does not differ greatly in different species, it is likely that a similar situation exists in humans.

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