摘要
早期药代动力学评价是药物发现过程的重要组成部分,可在药物发现早期对化合物的体内药动学特性进行区分,从而有针对性地进行研究,加快研发进程。新靶点及新化合物合成和筛选技术的进步,可供筛选的化合物数量快速增加,使药代动力学筛选速度成为新药研发的严重瓶颈。采用基于液相色谱质谱联用技术(LC-MS/MS)的盒式给药方法,即几种候选化合物混合后同时给单一动物进行快速样品分析,可增加化合物在体内的药代动力学筛选通量。盒式给药方法在节省实验资源和提高通量方面具有优势,但可能出现化合物相互作用,因此需要进行评价和验证,建立适当的盒式给药分析方法。盒式给药的方法已经得到较为广泛的应用,本文对近年来的盒式给药文献报道进行综述,并对其发展进行了展望。
Early pharmacokinetic evaluation is an important part of drug discovery,and should be conducted early in the process so that those compounds with the best pharmacokinetic characteristics are prioritized to speed up the development process.The advances of new targets discovery,new compound synthesis and screening technology produce a large number of compounds available for screening.The speed of pharmacokinetic analysis has therefore become a serious bottleneck.Cassette dosing,which involves the simultaneous administration of several compounds to a single animal followed by rapid sample analysis by liquid chromatography tandem mass spectrometry（LC-MS / MS）,is developed to increase the throughput of in vivo pharmacokinetic screening.The advantages of cassette dosing are saving experimental resources and improving the screening throughput so it.However the method of cassette dosing needs to be evaluated and validated to examine the possibility of compound interactions.This paper reviewed the literature of cassette dosing,and prospect of its development.
出处
《国际药学研究杂志》
CAS
2012年第6期488-492,共5页
Journal of International Pharmaceutical Research
