Reversible and Time-Dependent Inhibition of CYP3A4-Mediated Nifedipine Oxidation by Noscapine

	Reversible and Time-Dependent Inhibition of CYP3A4-Mediated Nifedipine Oxidation by Noscapine
	Jin, Xue-Li 1; Tang, Shu-Hong 3; Fang, Zhong-Ze 2; Qu, Yan-Qing 1; Liang, Rui 1; Gao, Zhen-Ming 1; Tang, Bo 1; Sun, De-Guang 1; Li, Ming 3; Yang, Ling 2
刊名	latin american journal of pharmacy
	2011-11-01
卷号	30 期号:9 页码:1854-1857
关键词	Drug-drug interaction (DDI) Nifedipine Noscapine Substrate-dependent inhibition Time-dependent inhibition (TDI) Warfarin
英文摘要	substrate-dependent inhibition of cyp3a4 might influence the extrapolation of drug interactions from the in vitro to in vivo situation. the aim of the present study is to investigate reversible and time-dependent inhibition of cyp3a4-mediated nifedipine oxidation by noscapine. furthermore, in vitro-in vivo extrapolation (ivive) was performed using in vitro parameters. the results showed that cyp3a4-mediated nifedipine oxidation activity was strongly inhibited with an ic50 of 25.7 +/- 5.4 mu m. kinetic analysis showed that inhibition of cyp3a4-mediated nifedipine oxidation by noscapine was best fit to a non-competitive manner with ki value of 10.9 mu m. ic50 shift experiment showed that ic50 was significantly decreased from 25.7 +/- 5.4 mu m to 0.34 +/- 0.07 mu m after pre-incubation with noscapine for 30 min, which indicated that time-dependent inhibition existed for inhibition of cyp3a4 by noscapine. the auc of (r)-warfarin was predicted to increase by 0.5 % using c-max or 0.2 % using unbound c-max with reversible inhibition prediction equation, while the auc of (r)-warfarin was estimated to increase by 23.1 % using c-max or 10.4 % using unbound c-max with tdi prediction equation. inhibition of cyp3a4 by noscapine showed substrate-dependent inhibition behaviour. however, the results obtained from ivive are very similar using testosterone or nifedipine as probe substrates.
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	pharmacology & pharmacy
研究领域[WOS]	pharmacology & pharmacy
关键词[WOS]	drug-drug interactions ; metabolism ; prediction ; warfarin ; cyp3a4 ; apoptosis ; binding ; cells
收录类别	SCI
语种	英语
WOS记录号	WOS:000301966100029
公开日期	2015-11-17
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/142313]
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 2, Dalian 116023, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 3.Fifth Hosp Dalian, Dept Med Oncol, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Jin, Xue-Li,Tang, Shu-Hong,Fang, Zhong-Ze,et al. Reversible and Time-Dependent Inhibition of CYP3A4-Mediated Nifedipine Oxidation by Noscapine[J]. latin american journal of pharmacy,2011,30(9):1854-1857.
APA	Jin, Xue-Li.,Tang, Shu-Hong.,Fang, Zhong-Ze.,Qu, Yan-Qing.,Liang, Rui.,...&Wang, Li-Ming.(2011).Reversible and Time-Dependent Inhibition of CYP3A4-Mediated Nifedipine Oxidation by Noscapine.latin american journal of pharmacy,30(9),1854-1857.
MLA	Jin, Xue-Li,et al."Reversible and Time-Dependent Inhibition of CYP3A4-Mediated Nifedipine Oxidation by Noscapine".latin american journal of pharmacy 30.9(2011):1854-1857.