Mueller Silke C, Majcher-Peszynska Jolanta, Mundkowski Ralf G, Uehleke Bernhard, Klammt Sebastian, Sievers Hartwig, Lehnfeld Romanus, Frank Bruno, Thurow Kerstin, Kundt Guenther, Drewelow Bernd
Center of Pharmacology and Toxicology, Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, 18057 Rostock, Germany.
Eur J Clin Pharmacol. 2009 Jan;65(1):81-7. doi: 10.1007/s00228-008-0554-y. Epub 2008 Sep 3.
Induction of CYP3A by St. John's wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function.
Twenty healthy male volunteers received an SJW powder with low hyperforin content for 2 weeks. Midazolam plasma concentration time profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication.
Midazolam AUC(0-infinity) slightly decreased from 124.0 +/- 62.5 ng/ml.h at baseline to 105.6 +/- 53.2 ng/ml.h after SJW (P < 0.05), representing a mean 11.3% decrease (95% CI: -22.8 to 0.21). No significant change in midazolam C(max), t(1/2) and t(max) was observed. For all pharmacokinetic parameters, the 90% CI for the geometric mean ratio of treatment over baseline were within the no-effect boundaries of 0.70-1.43.
Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant.
富含金丝桃素的圣约翰草（SJW）产品对细胞色素P450 3A（CYP3A）的诱导作用已有充分描述。由于CYP3A的诱导作用由金丝桃素以浓度依赖方式介导，且不同SJW制剂的金丝桃素含量差异显著，本研究旨在评估低金丝桃素含量的SJW粉末对CYP3A功能的影响。
20名健康男性志愿者服用低金丝桃素含量的SJW粉末2周。在SJW用药前一天和用药第14天单次口服7.5 mg咪达唑仑后，对咪达唑仑血浆浓度-时间曲线进行特征分析。
咪达唑仑的药时曲线下面积（AUC(0-∞)）从基线时的124.0±62.5 ng/ml·h略有下降至服用SJW后的105.6±53.2 ng/ml·h（P<0.05），平均下降11.3%（95%置信区间：-22.8至0.21）。咪达唑仑的峰浓度（C(max)）、半衰期（t(1/2)）和达峰时间（t(max)）未观察到显著变化。对于所有药代动力学参数，治疗组与基线组几何平均比值的90%置信区间在0.70-1.43的无效应范围内。
服用低金丝桃素含量的SJW产品导致CYP3A轻度诱导，临床认为无相关性。
