Background.- Grapefruit juice increases the bioavailability of several drugs known to be metabolized by CYP3A enzymes. Ketoconazole and itraconazole can increase the area under the concentration-time curve [AUC] of triazolam, a substrate of CYP3A, by more than twenty times.

Methods.- In this randomized crossover study the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of triazolam was investigated. Ten healthy young subjects received a single 0.25 mg dose of triazolam with either 250 mL grapefruit juice or water. Plasma concentrations and effects of triazolam were measured up to 17 hours.

Results. Grapefruit juice increased the (AUC) of triazolam in each subject and the peak concentration in nine of the 10 subjects. The mean AUC of triazolam was increased 1.5-fold (p<0.001) and the peak concentration was increased 1.3-fold (p<0.05) by grapefruit juice. Grapefruit juice postponed the peak time of triazolam from 1.6 hours to 2.5 hours (p<0.05). Grapefruit juice increased the effects of triazolam slightly; drowsiness was significantly (p< 0.05) enhanced.

Conclusions. Grapefruit juice can increase the plasma concentrations and effects of oral triazolam.

(CLIN PHARMACOL THER, 1995;58:127-31.)