体外试验预测药物代谢及相互作用的方法及数学分析模型研究进展.pdfVIP

中国药师　 　 2014年第17卷第9期　 　 China Pharmacist2014,Vol.17　 No.9 体外试验预测药物代谢及相互作用的方法及数学分析模型研 究进展 刘一峰　 (上海市静安区中心医院　 上海200040) 摘　 要　 目的:为新药的开发、已上市药物的结构改造以及一线临床联合用药方案的制定提供依据。 方法:检索CHKD及 PubMed数据库,分别以细胞色素、相互作用、体外试验为关键词进行检索,对2003~2013年的相关文献进行总结。 分析细胞 色素氧化酶的生物学特性以及如何选择合适的酶系统对药物进行体外代谢的药动学研究,以便推导其体内相互作用的可能 性。 结果:[I]/ K 值与药物相互作用的潜在可能性密切相关,但[I]值的估算是难点,应针对具体情况进行灵活调整。结论:i 以体外试验预测药物代谢及相互作用的技术能最大程度地避免繁琐的体内研究,可缩短新药研发周期,降低经济成本,并为 临床合理联合用药提供理论依据并及时反馈风险警示。 关键词　 细胞色素;药物相互作用;体外试验 中图分类号:R969.2 　 　 文献标识码:A　 　 文章编号:1008-049X(2014)09-1569-04 Study Progress in Methods and Mathematical Models for the Prediction of Drug Metabolism and Interac- tions on the Basis of in vitro Investigations Liu Yifeng (Central Hospital of Jingan District,Shanghai200040,China) ABSTRACT　 Objective:To provide the evidence for the development of new drugs,the modification in chemical structures of the registered drugs and the establishment of the therapeutic treatment involving several drugs. Method:Using cytochrome,drug interac- tion andinvitro investigationsasthekeywords,CHKDandPubMedwere searched,andthecorrespondingreferenceswere summarized from2003to2013. Thebiologicalcharactersofthecytochromeoxidaseandthewaysonthechoiceofthesuitableenzymesystemforthe research of drug invitro pharmacokinetic parameters were analyzed in order to predict the potential drug interactions in vivo.Result: The [I]/ K value had close relation with the possibility of the potential interactions,however,the calculation of [I]was the difficulti point,and the methods shouldbemodified accordingtothe specific situation. Conclusion:Thepredictiontechnology of drug metabo- lism and interactions on the basis of invitro investigations can avoid the invivo complicated process to the greatest extent,reduce the cycle time andthe economic costfor thenew drug development,andprovidethelogical evidence andtherisky levelfor thereasonable application of clinical drugs. KEY WORDS　 Cytochrome;Drug interaction;Invitro investigations 　 　 药物最