2001 Volume 16 Issue 5 Pages 466-477
More than 30% of the cases of discontinuation 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 properties, 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 development. 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 technologies 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 a large number of compounds in a relatively short period of time. The use of LC-MS/MS also greatly contributes to the reduction of the time required for in vivo animal PK studies.
This paper will focus on the successful management and strategies in early DMPK research from the perspectives of the pharmaceutical industry.
