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.
Hukkinen
S K
SK
Department of Clinical Pharmacology, University of Helsinki, Finland.
Varhe
A
A
Olkkola
K T
KT
Neuvonen
P J
PJ
D000284:Administration, Oral; D000328:Adult; D001628:Beverages; D001682:Biological Availability; D002957:Citrus; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D012016:Reference Values; D012894:Sleep Stages / Q000187:drug effects; D014229:Triazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D014229:Triazolam; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A