Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers
Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers
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DOI：
10.1177/00912709922007499
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发表时间：
1999-01-01
影响因子：
2.9
通讯作者：
Bekersky, I
中科院分区：
文献类型：
--
作者：
Hebert, MF;Fisher, RM;Bekersky, I
他克莫司是一种市售的免疫抑制剂，用于肝脏和肾脏移植。通过CYP 3A 4进行广泛代谢，是β-糖蛋白介导转运的底物。在6名健康男性志愿者中评价了利福平（一种抗结核药物和CYP 3A 4和β-糖蛋白的强效诱导剂）与他克莫司的药代动力学相互作用。他克莫司以0.1 mg/kg经口和0.025 mg/kg/4小时静脉给药。他克莫司的药代动力学是从18天伴随利福平给药期之前和期间单次经口和静脉给药后96小时内采集的系列血样中获得的。利福平联合给药显著增加了他克莫司的清除率（36.0 +/- 8.2 ml/hr/kg vs. 52.8 +/- 9.6 ml/hr/kg，p = 0.03），降低了他克莫司的生物利用度（14.4% +/- 5.7% vs. 7.0% +/- 2.7%; p = 0.03）。利福平似乎可诱导他克莫司的肠和肝代谢，最可能是通过诱导肝脏和小肠中的CYP 3A和β-糖蛋白。临床药理学杂志，1999;39：91-96（C）1999美国临床药理学学会.
Tacrolimus is a marketed immunosuppressant used in liver and kidney transplantation. It is subject to extensive metabolism by CYP3A4 and is a substrate for beta-glycoprotein-mediated transport. A pharmacokinetic interaction with rifampin, an antituberculosis agent and potent inducer of CYP3A4 and beta-glycoprotein, and tacrolimus was evaluated in six healthy male volunteers. Tacrolimus was administered at doses of 0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected over 96 hours, after single oral and intravenous administration prior to and during an 18-day concomitant rifampin dosing phase. Coadministration of rifampin significantly increased tacrolimus clearance (36.0 +/- 8.2 ml/hr/kg vs. 52.8 +/- 9.6 ml/hr/kg p = 0.03) and decreased tacrolimus bioavailability (14.4% +/- 5.7% vs. 7.0% +/- 2.7%; p = 0.03). Rifampin appears to induce both intestinal and hepatic metabolism of tacrolimus, most likely through induction of CYP3A and beta-glycoprotein in the liver and small bowel. Journal of Clinical pharmacology, 1999;39:91-96 (C) 1999 the American College of Clinical pharmacology.