alexa Effect of St John's wort on the pharmacokinetics of fexofenadine.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Wang Z, Hamman MA, Huang SM, Lesko LJ, Hall SD

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Abstract BACKGROUND: St John's wort is a popular over-the-counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P-glycoprotein. The effect of St John's wort on P-glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug. METHODS: A 3-period, open-label, fixed-schedule study design was used. Fexofenadine, 60 mg, was administered orally before administration of St John's wort, with a single dose of St John's wort (900 mg), and after 2 weeks of treatment with St John's wort (300 mg 3 times a day) to determine P-glycoprotein activity. RESULTS: A single dose of St John's wort significantly (P <.05) increased the maximum plasma concentration of fexofenadine by 45\% and significantly (P <.05) decreased the oral clearance by 20\%, with no change in half-life or renal clearance. Long-term administration of St John's wort did not cause a significant change in fexofenadine disposition relative to the untreated phase. Compared with the single-dose treatment phase, long-term St John's wort caused a significant 35\% decrease (P <.05) in maximum plasma concentration and a significant 47\% increase (P <.05) in fexofenadine oral clearance. CONCLUSIONS: A single dose of St John's wort resulted in a significant inhibition of intestinal P-glycoprotein. Long-term treatment with St John's wort reversed the changes in fexofenadine disposition observed with single-dose administration. This article was published in Clin Pharmacol Ther and referenced in Journal of Bioequivalence & Bioavailability

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