圣约翰草（贯叶连翘）对健康志愿者中他克莫司药代动力学的影响。

Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers.

作者信息

Hebert Mary F, Park Jeong M, Chen Yu-Luan, Akhtar Shahzad, Larson Anne M

机构信息

University of Washington, Department of Pharmacy, Seattle, WA 98195-7630, USA.

出版信息

J Clin Pharmacol. 2004 Jan;44(1):89-94. doi: 10.1177/0091270003261078.

DOI:10.1177/0091270003261078

PMID:14681346

Abstract

Tacrolimus is an immunosuppressant approved for the prevention of rejection following transplantation and is a substrate for CYP3A and P-glycoprotein. A pharmacokinetic interaction between St. John's wort (antidepressant herbal product and inducer of CYP3A and P-glycoprotein) and tacrolimus was evaluated in 10 healthy volunteers. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected following single oral doses (0.1 mg/kg) prior to and during an 18-day concomitant St. John's wort dosing phase (300 mg orally three times daily). Coadministration of St. John's wort significantly decreased tacrolimus AUC (306.9 microg.h/L +/- 175.8 microg.h/L vs. 198.7 microg.h/L +/- 139.6 microg.h/L; p=0.004) and increased apparent oral clearance (349.0 mL/h/kg +/- 126.0 mL/h/kg vs. 586.4 mL/h/kg +/- 274.9 mL/h/kg; p=0.01) and apparent oral volume of distribution at steady state (11.5 L/kg +/- 4.3 L/kg vs. 17.6 L/kg +/- 9.6 L/kg; p=0.04). St. John's wort appears to induce tacrolimus metabolism, most likely through induction of CYP3A and P-glycoprotein.

摘要

他克莫司是一种被批准用于预防移植后排斥反应的免疫抑制剂，是细胞色素P450 3A（CYP3A）和P-糖蛋白的底物。在10名健康志愿者中评估了圣约翰草（一种抗抑郁草药产品，也是CYP3A和P-糖蛋白的诱导剂）与他克莫司之间的药代动力学相互作用。他克莫司的药代动力学数据来自于在18天的圣约翰草联合给药阶段（每日口服3次，每次300mg）之前和期间单次口服剂量（0.1mg/kg）后采集的系列血样。圣约翰草的共同给药显著降低了他克莫司的曲线下面积（AUC）（306.9μg·h/L±175.8μg·h/L对比198.7μg·h/L±139.6μg·h/L；p=0.004），增加了表观口服清除率（349.0mL/h/kg±126.0mL/h/kg对比586.4mL/h/kg±274.9mL/h/kg；p=0.01）以及稳态下的表观口服分布容积（11.5L/kg±4.3L/kg对比17.6L/kg±9.6L/kg；p=0.04）。圣约翰草似乎诱导了他克莫司的代谢，很可能是通过诱导CYP3A和P-糖蛋白来实现的。