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

被引:38
|
作者
Penzak, SR
Gubbins, PO
Gurley, BJ
Wang, PL
Saccente, M
机构
[1] Mercer Univ, So Sch Pharm, Dept Pharm Practice, Atlanta, GA 30341 USA
[2] Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Coll Med, Dept Internal Med, Div Infect Dis, Little Rock, AR 72205 USA
关键词
itraconazole; grapefruit juice; CYP3A4; absorption;
D O I
10.1097/00007691-199906000-00009
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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 ng.hr/ml versus 1434 ng.hr/ml, p = 0.046) and a 47% decrease in the mean hydroxy-itraconazole AUC(0-72) (7264 ng.hr/ml versus 3880 ng.hr/mL, 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.
引用
收藏
页码:304 / 309
页数:6
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