Identification of phenobarbital N-glucosides as urinary metabolites of phenobarbital in mice

Authors

  • William H. Soine,

    Corresponding author
    1. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298–0581
    • Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298–0581
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  • Phyllis J. Soine,

    1. Bureau of Forensic Science, Division of Consolidated Laboratory Services, Commonwealth of Virginia, Richmond, VA 23219
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  • Terry M. England,

    1. Bureau of Forensic Science, Division of Consolidated Laboratory Services, Commonwealth of Virginia, Richmond, VA 23219
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  • John W. Ferkany,

    1. NOVA Pharmaceutical Corporation, CNS Pharmacology, 6200 Freeport Centre, Baltimore, MD 21224–2788
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  • Bruce E. Agriesti

    1. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298–0581
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Abstract

Previously, the N-glucosylation of phenobarbital had been observed only in humans. The results of a species screen (mouse, rat, guinea pig, rabbit, cat, dog, pig, and monkey) found that only mice excreted the N-glucosides of phenobarbital in urine after ip administration of sodium phenobarbital. The major diastereomer excreted by the mouse had the R configuration at the C-5 position of the barbiturate ring. The N-glucoside metabolites accounted for a small percentage of the dose (∼0.5%). Following ip dosing of the mouse with the phenobarbital N-glucosides, free phenobarbital could be detected in the urine. Upon ip or intercerebroventricular (icv) injection of the phenobarbital N-glucosides, minimal CNS activity was observed in the mouse.

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