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.