Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers

Penzak, S. R.;Gubbins, P. O.;Gurley, B. J.;Wang, P. L.;Saccente, M.

Author address: 

Penzak, SR, Mercer Univ, So Sch Pharm, Dept Pharm Practice, 3001 Mercer Univ Dr, Atlanta, GA 30341 USA


The systemic availability of itraconazole capsules may be reduced secondary to elevated gastric pH and possibly by presystemic intestinal metabolism via CYP3A4. Grapefruit juice is acidic and an inhibitor of intestinal CYP3A4. To determine the effect of grapefruit juice on the systemic availability of itraconazole capsules, serum itraconazole and hydroxy- itraconazole concentrations were determined in eleven healthy volunteers studied in a randomized, two-way crossover design. Concurrent grapefruit juice resulted in a 43% decrease in the mean itraconazole AUG(0-48) (2507 versus 1434, p = 0.046) and a 47% decrease in the mean hydroxy- itraconazole AUC(0-72) (7264 versus 3880, p = 0.025. Grapefruit juice also significantly increased the mean itraconazole T-max (5.5 versus 4 hours). We conclude that concomitant grapefruit juice does not enhance the systemic availability of itraconazole capsules, but rather appears to impair itraconazole absorption. Therefore, concomitant grapefruit juice will not likely be useful in improving the oral availability of itraconazole capsules.

abstract No: 


Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th