Induction of Fluconazole Metabolism by Rifampin: In Vivo Study in Humans

The effects of rifampin on the pharmacokinetics of fluconazole were analyzed in an open-label, placebo-controlled, parallel study. Sixteen healthy male volunteers, randomized into two groups, received 200 mg of oral fluconazole on days 1 and 22. On days 8 through 27, group I received oral rifampin, 600 mg/d, and group II received placebo. Fluconazole in serum was analyzed by HPLC. On days 1 and 22, respectively, the AUC (μg · hr/mL) (mean ± SD) was 160.5 ± 19.5 and 124 ± 22.2 in group I, 152 ± 25 and 152.8 ± 33.9 in group II; the Kel (hr−1) was .0211 ± .0030 and .0264 ± .0040 in group I, .0219 ± .0036 and .0216 ± .0053 in group II. Cmax and Tmax did not change significantly in either group. Urinary 6β-hydroxycortisol/cortisol increased from 3.47 ± 1.04 to 15.2 ± 5.07 in group I, but was unchanged (3.54 ± 1.33–4.26 ± 2.36) in group II on days 1 and 22, respectively. The findings in this study indicate that rifampin induces the metabolism of fluconazole.