Activation of CYP3A-mediated testosterone 6β-hydroxylation by tanshinone IIA and midazolam 1-hydroxylation by cryptotanshinone in human liver microsomes

被引：7
作者：
Qiu, Furong [2 ]
Zhang, Rong [1 ]
Wang, Guangji [1 ]
Gao, Chenglu [2 ]
Sun, Jianguo [1 ]
Jiang, Jian [2 ]
Ma, Yueming [3 ]
机构：
[1] China Pharmaceut Univ, Key Kab Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Clin Pharmacokinet Lab, Shanghai, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai, Peoples R China
来源：
XENOBIOTICA | 2010年 / 40卷 / 12期
关键词：
Tanshinone IIA; cryptotanshinone; activation; CYP3A; testosterone; midazolam; CYTOCHROME-P450; 3A4; IN-VITRO; ALPHA-NAPHTHOFLAVONE; CATALYTIC-ACTIVITY; DRUG-INTERACTIONS; DANSHEN EXTRACT; ACTIVE-SITE; CYP3A4; COOPERATIVITY; METABOLISM;
D O I：
10.3109/00498254.2010.519062
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
1. This study evaluated the in vitro activation of CYP3A-mediated midazolam 1-hydroxylation and testosterone 6 beta-hydroxylation by tanshinone I, tanshinone IIA, and cryptotanshinone. 2. The abilities of tanshinones to activate CYP3A-mediated midazolam 1-hydroxylation and testosterone 6 beta-hydroxylation in human liver microsomes (HLMs) were tested. Substrate-and effector-dependent activation of CYP3A by tanshinones were both observed. 3. 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 6 beta-hydroxylation, whereas cryptotanshinone and tanshinone I did not. 4. 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.
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页码：800 / 806
页数：7
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