Effect of metronidazole on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy male volunteers

Kyoung Ah Kim, Ji Young Park

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Objective Metronidazole has been reported to cause various drug interactions when co-administered with certain drugs. One possible mechanism for this action is through an inhibition of P-glycoprotein (P-gp). We have assessed the possible inhibitory effects of metronidazole on P-gpmediated drug disposition in healthy subjects using fexofenadine as a P-gp substrate. Methods This was a randomized, placebo-controlled, openlabel, two-way crossover study involving 12 healthy male volunteers who were treated with metronidazole 500 mg or placebo three times daily for 7 days. On day 7, a single dose of fexofenadine 120 mg was given orally. Plasma levels of fexofenadine were measured and its pharmacokinetics assessed. Results: Metronidazole did not affect the plasma concentration profiles and the pharmacokinetics of fexofenadine. The area under the time versus concentration curve of fexofenadine in the metronidazole phase (2075.7 ng h/mL) was similar to that of the placebo phase (1999.2 ng h/mL) (P=0.356). Additionally, metronidazole did not affect the maximum plasma levels of fexofenadine (304.4 ng/mL for placebo vs. 293.2 ng/mL for metronidazole) (P=0.423). The elimination half-life and oral clearance of fexofenadine were not affected by metronidazole treatment. Conclusion These results show that metronidazole did not have any inhibitory effect on the pharmacokinetics of fexofenadine. The results of the present study provide evidence that metronidazole does not act as an inhibitor of P-gp-mediated disposition in humans.

    Original languageEnglish
    Pages (from-to)721-725
    Number of pages5
    JournalEuropean Journal of Clinical Pharmacology
    Volume66
    Issue number7
    DOIs
    Publication statusPublished - 2010 Jul

    Keywords

    • Drug interaction
    • Fexofenadine
    • Metronidazole
    • P-glycoprotein

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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