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 (micrograms.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 6 beta-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.
Apseloff
G
G
Department of Pharmacology, College of Medicine, Ohio State University, Columbus.
Hilligoss
D M
DM
Gardner
M J
MJ
Henry
E B
EB
Inskeep
P B
PB
Gerber
N
N
Lazar
J D
JD
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004334:Drug Administration Schedule; D015725:Fluconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*
C001380:6 beta-hydroxycortisol; D015725:Fluconazole; D012293:Rifampin; D006854:Hydrocortisone