Mueller Silke C, Majcher-Peszynska Jolanta, Uehleke Bernhard, Klammt Sebastian, Mundkowski Ralf G, Miekisch Wolfram, Sievers Hartwig, Bauer Steffen, Frank Bruno, 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. 2006 Jan;62(1):29-36. doi: 10.1007/s00228-005-0061-3. Epub 2005 Dec 10.
Induction of CYP3A by St. John's wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content.
Forty-two male, healthy volunteers were randomized into six parallel SJW medication groups with varying composition especially with regard to HYF content. Midazolam plasma concentration 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.
All SJW preparations tested resulted in a decrease in midazolam AUC, although the extent of the effect differed. The extract LI 160 (HYF 41 mg/day) decreased midazolam AUC0-12h by 79.4% (95% CI -88.6; -70.1), which was significantly greater than the effect by any other medication (p<0.05). SJW powder tablets 2.7 g/day (HYF 12 mg/day) resulted in a midazolam AUC0-12h decrease of 47.9% (95% CI -59.7;-36.2), while 2.7 g/day SJW powder tablets that were almost devoid of HYF (0.13 mg/day) reduced midazolam AUC0-12h by only 21.1% (95% CI -33.9; -8.3). Considering all six SJW medications tested, the extent of midazolam AUC decrease correlated significantly with increasing HYF dose (r=-0.765, p<0.001), but not with hypericin dose (r=-0.067; p=0.673).
The extent of induction of CYP3A varies among St. John's wort products and depends on hyperforin dose.
富含金丝桃素（HYF）的圣约翰草（SJW）提取物对细胞色素P450 3A（CYP3A）的诱导作用已有充分描述。由于SJW产品中HYF及其他主要成分的含量各不相同，本研究旨在评估HYF含量从极低到极高的SJW制剂对CYP3A功能的影响。
42名健康男性志愿者被随机分为6个平行的SJW用药组，其成分各异，尤其是HYF含量不同。在SJW用药前一天和用药第14天，单次口服7.5mg咪达唑仑后，对咪达唑仑血浆浓度曲线进行特征分析。
所有测试的SJW制剂均导致咪达唑仑药时曲线下面积（AUC）降低，尽管其作用程度有所不同。LI 160提取物（HYF 41mg/天）使咪达唑仑AUC0 - 12h降低79.4%（95%置信区间 - 88.6；- 70.1），这显著大于其他任何药物的作用（p < 0.05）。2.7g/天的SJW分散片（HYF 12mg/天）使咪达唑仑AUC0 - 12h降低47.9%（95%置信区间 - 59.7；- 36.2），而几乎不含HYF（0.13mg/天）的2.7g/天SJW分散片仅使咪达唑仑AUC0 - 12h降低21.1%（95%置信区间 - 33.9；- 8.3）。综合所有6种测试的SJW药物，咪达唑仑AUC降低程度与HYF剂量增加显著相关（r = - 0.765，p < 0.001），但与金丝桃素剂量无关（r = - 0.067；p = 0.673）。
圣约翰草产品对CYP3A的诱导程度各不相同，且取决于金丝桃素剂量。
