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Research ArticleArticle

Effect of Garlic, Gingko, and St. John’s Wort Extracts on the Pharmacokinetics of Fexofenadine: A Mechanistic Study

Jasmina Turkanovic, Michael B. Ward, Jacobus P. Gerber and Robert W. Milne
Drug Metabolism and Disposition May 2017, 45 (5) 569-575; DOI: https://doi.org/10.1124/dmd.116.073528
Jasmina Turkanovic
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
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Michael B. Ward
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
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Jacobus P. Gerber
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
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Robert W. Milne
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
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Abstract

The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John’s wort (SJW; 1000 mg/kg; positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines divided into four segments (SI–SIV) and analyzed for P-gp and Oatp1a5. In vivo, SJW increased the clearance of i.v. administered fexofenadine by 28%. Garlic increased the area under the curve0–∞ and maximum plasma concentration of orally administered fexofenadine by 47% and 85%, respectively. Ginkgo and SJW had no effect on the oral absorption of fexofenadine. In the perfused liver, garlic, ginkgo, and SJW increased the biliary clearance of fexofenadine with respect to perfusate by 71%, 121%, and 234%, respectively. SJW increased the biliary clearance relative to the liver concentration by 64%. The ratio of liver to perfusate concentrations significantly increased in all treated groups. The expression of Oatp1a5 in SI was increased by garlic (88%) and SJW (63%). There were no significant changes in the expression of P-gp. Induction of intestinal Oatp1a5 by garlic may explain the increased absorption of orally administered fexofenadine. Ginkgo had no effect on the expression of intestinal P-gp or Oatp1a5. A dual inductive effect by SJW on opposing intestinal epithelial transport by Oatp1a5 and P-gp remains a possibility.

Footnotes

    • Received September 20, 2016.
    • Accepted February 6, 2017.
  • https://doi.org/10.1124/dmd.116.073528.

  • Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 45 (5)
Drug Metabolism and Disposition
Vol. 45, Issue 5
1 May 2017
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Research ArticleArticle

Effect of Herbal Extracts on Fexofenadine Pharmacokinetics

Jasmina Turkanovic, Michael B. Ward, Jacobus P. Gerber and Robert W. Milne
Drug Metabolism and Disposition May 1, 2017, 45 (5) 569-575; DOI: https://doi.org/10.1124/dmd.116.073528

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Research ArticleArticle

Effect of Herbal Extracts on Fexofenadine Pharmacokinetics

Jasmina Turkanovic, Michael B. Ward, Jacobus P. Gerber and Robert W. Milne
Drug Metabolism and Disposition May 1, 2017, 45 (5) 569-575; DOI: https://doi.org/10.1124/dmd.116.073528
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