Effects of rifampin on the disposition of gepirone ER and its metabolites

Y. W.Francis Lam, Larry Ereshefsky, Andreas Port, Cees J. Timmer, Peter Dogterom

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1 Scopus citations


Objective: To investigate the effects of rifampin on the steady-state pharmacokinetics of gepirone and metabolites after multiple dosing of both drugs. Methods: 24 subjects completed a randomized crossover study with 2 study phases separated by a washout period of at least 4 weeks. The subjects received multiple dosing of gepirone extended-release (gepirone ER) (20 mg daily for 2 days titrated to 40 mg daily for 5 days) with and without concurrent use of rifampin 600 mg daily. Plasma concentrations of gepirone and two principal metabolites were determined for up to 48 hours after dosing on day 7. Urinary 6β-hydroxycortisol:cortisol ratio was also used to assess the extent of enzyme induction during both study periods. Results: Rifampin significantly decreased the area under the plasma concentration-time curves (AUC) of gepirone and 3′-OH-gepirone by 95% and 65%, respectively. The peak concentration (Cmax) values also were reduced by 92% and 58%, respectively. On the other hand, there were minimal changes in AUC and Cmax of 1-PP during concurrent use of rifampin. Gepirone dosing did not change the urinary 6β-hydroxycortisol:cortisol ratio, in contrast to a 4.1-fold increase in the ratio with concurrent use of rifampin. Conclusions: Rifampin significantly decreased the systemic exposure of gepirone and 3′-OH-gepirone. The likely mechanism is induction of CYP3A4-mediated first-pass metabolism in the intestine and the liver. Concurrent use of potent CYP3A4 enzyme inducers might lead to significant reduction in pharmacologic effect of gepirone. On the other hand, gepirone does not appear to have CYP3A4 induction or inhibition effects.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalOpen Drug Metabolism Journal
StatePublished - 2009


  • Cytochrome P-450 3A4
  • Enzyme induction
  • Gepirone
  • Rifampin

ASJC Scopus subject areas

  • Pharmacology


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