Strategic approach for drug metabolism and pharmacokinetic research in the drug discovery process

摘要

More than 30% of the clinical development of new drugs.Unfavorable drug metabolism/pharmacokinetic properties (DMPK) are probably responsible for.Since the ideal medicine is blessed with a good balance of pharmacological potency/selectivity and DMPK properies,a compound with an inappropriate DMPK will never become an innovative patient-oriented drug.The ability to predict human DMPK early in the drug discovery process is,therefore,key in reducing the attrition rate of compounds entering dev4elopment.Moreover,by maximizing early DMPK studies,useful information and guidance for drug discovery programs can be provided to medicinal chemists and pharmacologists.Dramatic advances in technoklogies such as combinatorial chemistry and high throughput screening have been revolutionizing the drug discovery process over the past decade.This paradigm shift is having a great impact on traditional DMPK research and is driving the challenge for high throughput DMPK research.In vitro DMPK studies that use a variety of human tissues allow the screening of large number of compounds in a relativley short period of time.The use of LC-MS/MS also gre4atly contributes to the reduction of the time required for in vivo animal PK studies. This paper will focus ont he succesful management and strategies in early DMPK research from the perspectives of the pharmaceutical industry.