Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol

	Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol
	Qu, Yan-Qing 1; Fang, Zhong-Ze 2,3; Yang, Ling 2; Gao, Zhen-Ming 1; Liang, Rui 1; Zhu, Liang-Liang 2,3; Dong, Pei-Pei 2,3; Zhang, Yan-Yan 2,3; Ge, Guang-Bo 2; Wang, Li-Ming 1
刊名	pharmazie
	2011-03-01
卷号	66 期号:3 页码:216-221
ISSN号	待补充
通讯作者	li-mingwang
产权排序	2,2
中文摘要	reversible inhibition of four important human liver cytochrome p450 enzymes by diethylstilbestrol
英文摘要	diethylstilbestrol (des), a synthetic estrogen clinically used to treat threatened abortion between the 1940 s and the 1970s, has been restricted to treat certain cases of prostatic and breast cancer due to its adverse drug responses such as teratogenicity and carcinogenicity. some reports have demonstrated that the addition of des to docetaxel could modify tubulin composition and improve response of prostate cancer to chemotherapy. given that des might be co-administered with other drugs such as docetaxel, the present study focused on cyp-based drug-drug interaction (ddi). in vitro inhibitory effects of des on cyp isoforms were investigated, and the results showed that des could competitively inhibit cyp3a4, cyp2c8, cyp2c9 and cyp2e1. the inhibition constants (k(i)) were calculated to be 4.4 mu m, 3.0 mu m, 5.0 mu m and 8.0 mu m for cyp3a4, cyp2c9, cyp2e1 and cyp2c8, respectively. based on peak serum des level after drip influsion of 500 mg of fosfestrol (des diphosphate) in patients, [i]/k(i) was calculated to be 4.3, 6.2, 3.7 and 2.3 for cyp3a4, cyp2c9, cyp2e1 and cyp2c8, which suggested that des was likely to induce in vivo ddi through inhibition of these four major cyp isoforms. these results collectively demonstrate that adverse drug responses might exist when des is co-administered with other drugs.
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine ; physical sciences
类目[WOS]	chemistry, medicinal ; chemistry, multidisciplinary ; pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy ; chemistry
关键词[WOS]	drug-drug interactions ; prostate-cancer ; phase-ii ; metabolism ; toxicity ; warfarin ; tumors ; trial ; p450s
收录类别	SCI
语种	英语
WOS记录号	WOS:000290597700013
公开日期	2012-07-09
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/115813]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.Dalian Med Univ, Affiliated Hosp 1, Dalian, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China 3.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Qu, Yan-Qing,Fang, Zhong-Ze,Yang, Ling,et al. Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol[J]. pharmazie,2011,66(3):216-221.
APA	Qu, Yan-Qing.,Fang, Zhong-Ze.,Yang, Ling.,Gao, Zhen-Ming.,Liang, Rui.,...&Wang, Li-Ming.(2011).Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol.pharmazie,66(3),216-221.
MLA	Qu, Yan-Qing,et al."Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol".pharmazie 66.3(2011):216-221.