EFFECT OF GRAPEFRUIT JUICE ON PHARMACOKINETICS OF ITRACONAZOLE IN HEALTHY-SUBJECTS

Objective: To examine the effect of grapefruit juice on the dispositio n of oral administered itraconazole in healthy subjects. Methods: Twen ty-two healthy male subjects received a single 100 mg dose of itracona zole with either 350 ml grapefruit juice, orange juice or mineral wate r. Plasma concentrations of itraconazole were measured by HPLC, and ph armacokinetic parameters; C-max, T-max, T-1/2, AUC, and AUC corrected by human body surface area: AUC/S, were calculated. Results: Grapefrui t juice had no effect on any pharmacokinetic parameter of itraconazole . However, Tin, AUG, or AUC/S were significantly decreased in orange j uice treatment group compared to those in mineral water group (average decrease 56%, p < 0.01, 41%, p < 0.05, and 43%, p < 0.05, respectivel y). Conclusion: Coadministration of grapefruit juice did not affect an y pharmacokinetic parameter of itraconazole while that of orange juice decreased the parameters of T-1/2, AUC, and AUC/S of the drug.