Qiu Furong, Zhang Rong, Wang Guangji, Gao Chenglu, Sun Jianguo, Jiang Jian, Ma Yueming
Lab of Clinical Pharmacokinetics, Shuguang hospital, Shanghai University of Traditional Chinese Medicine, China.
Xenobiotica. 2010 Dec;40(12):800-6. doi: 10.3109/00498254.2010.519062. Epub 2010 Oct 22.
This study evaluated the in vitro activation of CYP3A-mediated midazolam 1-hydroxylation and testosterone 6β-hydroxylation by tanshinone I, tanshinone IIA, and cryptotanshinone. The abilities of tanshinones to activate CYP3A-mediated midazolam 1-hydroxylation and testosterone 6β-hydroxylation in human liver microsomes (HLMs) were tested. Substrate- and effector-dependent activation of CYP3A by tanshinones were both observed. Cryptotanshinone was shown to activate CYP3A-mediated midazolam 1-hydroxylation in a concentration-dependent manner. In contrast, tanshinone IIA and tanshinone I did not activate this hydroxylation reaction. In addition, tanshinone IIA activated CYP3A-mediated testosterone 6β-hydroxylation, whereas cryptotanshinone and tanshinone I did not. The results from our study enhance the understanding of CYP3A activation by tanshinone IIA and cryptotanshinone in HLMs. Additionally, these data allow for an accurate prediction of the magnitude and likelihood of Danshen-drug interactions.
本研究评估了丹参酮 I、丹参酮 IIA 和隐丹参酮对 CYP3A 介导的咪达唑仑 1-羟化和睾酮 6β-羟化的体外激活作用。测试了丹参酮在人肝微粒体（HLMs）中激活 CYP3A 介导的咪达唑仑 1-羟化和睾酮 6β-羟化的能力。观察到丹参酮对 CYP3A 的底物依赖性和效应物依赖性激活。隐丹参酮以浓度依赖性方式激活 CYP3A 介导的咪达唑仑 1-羟化。相比之下，丹参酮 IIA 和丹参酮 I 未激活此羟化反应。此外，丹参酮 IIA 激活 CYP3A 介导的睾酮 6β-羟化，而隐丹参酮和丹参酮 I 则未激活。我们的研究结果增进了对丹参酮 IIA 和隐丹参酮在 HLMs 中激活 CYP3A 的理解。此外，这些数据有助于准确预测丹参与药物相互作用的程度和可能性。
