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 journalArticle

11 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 1

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fexofenadine
Metronidazole
P-Glycoprotein
Healthy Volunteers
Pharmacokinetics
Placebos

Keywords

  • Drug interaction
  • Fexofenadine
  • Metronidazole
  • P-glycoprotein

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Effect of metronidazole on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy male volunteers",
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.",
keywords = "Drug interaction, Fexofenadine, Metronidazole, P-glycoprotein",
author = "Kim, {Kyoung Ah} and Ji-Young Park",
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language = "English",
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TY - JOUR

T1 - Effect of metronidazole on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy male volunteers

AU - Kim, Kyoung Ah

AU - Park, Ji-Young

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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.

AB - 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.

KW - Drug interaction

KW - Fexofenadine

KW - Metronidazole

KW - P-glycoprotein

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U2 - 10.1007/s00228-010-0797-2

DO - 10.1007/s00228-010-0797-2

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EP - 725

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 7

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