Effect of zolpidem on human Cytochrome P450 activity, and on transport mediated by P-glycoprotein

Authors

  • Lisa L. von Moltke,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
    2. Division of Clinical Pharmacology, Tufts-New England Medical Center, Boston MA, USA
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  • James L. Weemhoff,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
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  • Michael D. Perloff,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
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  • Leah M. Hesse,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
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  • Jerold S. Harmatz,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
    2. Division of Clinical Pharmacology, Tufts-New England Medical Center, Boston MA, USA
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  • Barbara F. Roth-Schechter,

    1. Boston Research and Science Consulting, Dover, MA, USA
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  • David J. Greenblatt

    Corresponding author
    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA
    2. Division of Clinical Pharmacology, Tufts-New England Medical Center, Boston MA, USA
    • Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA
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Abstract

The influence of high concentrations of zolpidem (100 μM, corresponding to approximately 200 times maximum therapeutic concentrations) on the activity of six human Cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Zolpidem produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. Transport of rhodamine 123, presumed to be mediated mainly by the energy-dependent efflux transport protein P-glycoprotein, was studied in a cell culture system using a human intestinal cell line. High concentrations of zolpidem (100 μM), exceeding the usual therapeutic range by more than 100-fold, produced only modest impairment of rhodamine 123 transport. The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport. Copyright © 2002 John Wiley & Sons, Ltd.

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