Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice

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(0-infinity)] 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(0-infinity) of triazolam in each subject and the peak concentration in nine of the 10 subjects. The mean AUC(0-infinity) 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.