Grapefruit juice substantially increases plasma concentrations of buspirone

Clin Pharmacol Ther. 1998 Dec;64(6):655-60. doi: 10.1016/S0009-9236(98)90056-X.


Background: Buspirone has a low oral bioavailability because of extensive first-pass metabolism. The effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of orally administered buspirone is not known.

Methods: In a randomized, 2-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water 3 times a day for 2 days. On day 3, each subject ingested 10 mg buspirone with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours after buspirone administration. Timed blood samples were collected up to 12 hours after ingestion, and the effects of buspirone were measured with 6 psychomotor tests up to 8 hours after ingestion.

Results: Grapefruit juice increased the mean peak plasma concentration of buspirone 4.3-fold (range, 2-fold to 15.6-fold; P < .01) and the mean area under the plasma buspirone concentration-time curve 9.2-fold (range, 3-fold to 20.4-fold; P < .01). The time of the peak concentration (tmax) of buspirone increased from 0.75 to 3 hours (P < .01), and the elimination half-life (t1/2) was slightly increased (P < .01) by grapefruit juice. A significant increase in the pharmacodynamic effects of buspirone by grapefruit juice was seen only in subjective overall drug effect (P < .01).

Conclusions: Grapefruit juice considerably increased plasma buspirone concentrations. The probable mechanism of this interaction is delayed gastric emptying and inhibition of the cytochrome P450 3A4-mediated first-pass metabolism of buspirone caused by grapefruit juice. Concomitant use of buspirone and at least large amounts of grapefruit juice should be avoided.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Beverages
  • Buspirone / blood*
  • Citrus*
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / drug effects
  • Female
  • Food-Drug Interactions
  • Half-Life
  • Humans
  • Male
  • Mixed Function Oxygenases / drug effects
  • Reference Values
  • Serotonin Receptor Agonists / blood*


  • Serotonin Receptor Agonists
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Buspirone