Grapefruit juice substantially increases plasma concentrations of buspirone.
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.
Lilja
J J
JJ
Department of Clinical Pharmacology, University of Helsinki, Finland.
Kivistö
K T
KT
Backman
J T
JT
Lamberg
T S
TS
Neuvonen
P J
PJ
D000328:Adult; D001628:Beverages; D002065:Buspirone / Q000097:blood*; D002957:Citrus; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000097:blood*
D017366:Serotonin Receptor Agonists; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D002065:Buspirone