老年心脏病学杂志（英文版）2009，Vol.6Issue(2)：115-118,4.
Inhibitory effects of amiodarone on simvastatin metabolism in human liver microsomes
Inhibitory effects of amiodarone on simvastatin metabolism in human liver microsomes
Chao Wan 1Jiang wei Zhang 1Ning Zhu 1Ling Yang1
作者信息
- 1. Medical Department No 2,Clinical Department No. 403, Hospital No. 210 of PLA , Dalian, Liaoning 116021, China
- 折叠
摘要
Abstract
Objective To investigate the effects ofamiodarone (AMD) on simvastatin (SV) in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were tested in HLM. The logarithm of relative inhibition values was plotted versus preincubation time (0, 5, 10, 15, 20min) for a series concentration of AMD used (0, 2, 5,25, 50 μ mol/L), and the slopes determined by linear regression. These slope values represente the observed inactivation rate constants (kobs). A double-reciprocal plot was then constructed using the reciprocal of the ko～ (y-axis) and the reciprocal of the associated inhibitor concentration (x-axis) to estimate the values ofkinact and K, which were two principal kinetic constants that were specific for mechanism-based inhibition (MBI).drug-drug interactions (DDI) potential was predicted based on in vitro data and by using the in vitro-in vivo extrapolation. Results The time-, concentration- and NADPH-dependent charactga'istics confirmed that when SV was the substrate of CYP3A4, the inhibition of AMD to CYP3A4 is MBI. Kj and kinact value were calculated to be 5.1 μ mol/L and 0.018min-1 The Clint of SV was reduced 2.96-5.63 fold when it was administrated with AMD. Conclusion Based on the results, AMD would inhibit SV metabolism via the mechanism-based manner, which would lead to DDI when they are taken together. Careful clinical observation is recommended when AMD and SV have to be simultaneously prescribed.关键词
amiodarone/simvastatin/CYP3A4/drug-drug interaction/mechanism-based inhibitionKey words
amiodarone/simvastatin/CYP3A4/drug-drug interaction/mechanism-based inhibition分类
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Chao Wan,Jiang wei Zhang,Ning Zhu,Ling Yang..Inhibitory effects of amiodarone on simvastatin metabolism in human liver microsomes[J].老年心脏病学杂志（英文版）,2009,6(2):115-118,4.
