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Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver

机译：贯叶连翘对灌注大鼠肝脏细胞色素P-450活性的影响

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摘要

St. John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and a herbal antidepressant that has been implicated in drug interactions with substrates of several cytochrome P-450 (CYP) isozymes. The effects of the St. John's wort extract (100 mg/kg, i.p., once daily for 10 days) on metabolic activity of CYP450 were assessed in the system of isolated perfused rat liver. The substrates used in this study were tolbutamide (CYP2C6), dextromethorphan (CYP2D2) and midazolam (CYP3A2). Validated HPLC method was used to quantify all compounds of interest. St. John's wort administration affected CYP activity, causing a significant decline in AUC of dextromethorphan [F(4,3 1)= 1511, p < 0.001; PLSD, p < 0.001] and AUC of midazolam [ F(3,25)=221, p < 0.001; PLSD, p =0.035] and a significant increase in AUC of tolbutamide [F(3,26)=200,p < 0.001; PLSD,p < 0.001]. St. John's wort administration resulted in a significant induction of CYP2D2 and CYP3A2, and in a significant inhibition of CYP2C6 metabolic activities. (c) 2005 Elsevier Inc. All rights reserved.
机译：圣约翰草（Hypericum perforatum）是一种流行的非处方膳食补充剂，是一种草药抗抑郁药，与药物与几种细胞色素P-450（CYP）同工酶的底物相互作用有关。在分离的灌注大鼠肝脏系统中评估了圣约翰草提取物（100 mg / kg，腹腔注射，每天一次，连续10天）对CYP450代谢活性的影响。本研究中使用的底物为甲苯磺丁酰胺（CYP2C6），右美沙芬（CYP2D2）和咪达唑仑（CYP3A2）。经验证的HPLC方法用于定量所有目标化合物。服用圣约翰草会影响CYP活性，导致右美沙芬的AUC显着下降[F（4,3 1）= 1511，p <0.001; PLSD，p <0.001]和咪达唑仑的AUC [F（3,25）= 221，p <0.001; PLSD，p = 0.035]和甲苯磺丁酰胺的AUC显着增加[F（3,26）= 200，p <0.001; PLSD，p ＜0.001]。圣约翰草的给药导致CYP2D2和CYP3A2的显着诱导，以及CYP2C6代谢活性的显着抑制。 （c）2005 Elsevier Inc.保留所有权利。

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