利福平对氟康唑代谢的诱导作用：人体体内研究

Induction of fluconazole metabolism by rifampin: in vivo study in humans.

作者信息

Apseloff G, Hilligoss D M, Gardner M J, Henry E B, Inskeep P B, Gerber N, Lazar J D

机构信息

Department of Pharmacology, College of Medicine, Ohio State University, Columbus.

出版信息

J Clin Pharmacol. 1991 Apr;31(4):358-61. doi: 10.1002/j.1552-4604.1991.tb03718.x.

DOI:10.1002/j.1552-4604.1991.tb03718.x

PMID:2037709

Abstract

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.

摘要

在一项开放标签、安慰剂对照的平行研究中，分析了利福平对氟康唑药代动力学的影响。16名健康男性志愿者被随机分为两组，在第1天和第22天接受200mg口服氟康唑。在第8天至第27天，第一组接受口服利福平，600mg/天，第二组接受安慰剂。通过高效液相色谱法分析血清中的氟康唑。在第1天和第22天，第一组的AUC（微克·小时/毫升）（平均值±标准差）分别为160.5±19.5和124±22.2，第二组为152±25和152.8±33.9；第一组的Kel（小时-1）为0.0211±0.0030和0.0264±0.0040，第二组为0.0219±0.0036和0.0216±0.0053。两组的Cmax和Tmax均无显著变化。在第1天和第22天，第一组尿中6β-羟基皮质醇/皮质醇从3.47±1.04增加到15.2±5.07，而第二组则无变化（3.54±1.33 - 4.26±2.36）。本研究结果表明，利福平可诱导氟康唑的代谢。