Grapefruit juice substantially increases plasma concentrations of buspirone

Background: Buspirone has a low oral bioavailability because of extensive f irst-pass metabolism, The effect of grapefruit juice on the pharmacokinetic s and pharmacodynamics of orally administered buspirone is not known, Methods: In a randomized, 2-phase crossover study, 10 healthy volunteers to ok either 200 mt double-strength grapefruit juice or water 3 times a day fo r 2 days. On day 3, each subject ingested 10 mg buspirone with either 200 m t grapefruit juice or water, and an additional 200 mt was ingested 1/2 hour and 1 1/2 hours after buspirone administration. Timed blood samples were c ollected 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 b uspirone 4.3-fold (range, 2-fold to 15.6-fold; P < .01) and the mean area u nder the plasma buspirone concentration-time curve 9.2-fold (range, 3-fold to 20.4-fold; P < .01), The time of the peak concentration (t(max)) of busp irone increased from 0.75 to 3 hours (P < .01), and the elimination half-li fe (t(1/2)) was slightly increased (P < .01) by grapefruit juice. A signifi cant increase in the pharmacodynamic effects of buspirone by grapefruit jui ce was seen only in subjective overall drug effect (P < .01), Conclusions Grapefruit juice considerably increased plasma buspirone concen trations. The probable mechanism of this interaction is delayed gastric emp tying and inhibition of the cytochrome P450 3A4-mediated first-pass metabol ism of buspirone caused by grapefruit juice. Concomitant use of buspirone a nd at least large amounts of grapefruit juice should be avoided.