The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery.
Major reasons preventing many early candidates reaching market are the inappropriate ADME (absorption, distribution, metabolism and excretion) properties and drug-induced toxicity. From a commercial perspective, it is desirable that poorly behaved compounds are removed early in the discovery phase rather than during the more costly drug development phases. As a consequence, over the past decade, ADME and toxicity (ADMET) screening studies have been incorporated earlier in the drug discovery phase. The intent of this review is to introduce the desirable attributes of a new chemical entity (NCE) to the medicinal chemist from an ADMET perspective. Fundamental concepts, key tools, reagents and experimental approaches used by the drug metabolism scientist to aid a modern project team in predicting human pharmacokinetics and assessing the "drug-like" molecule are discussed.
Lin
Jing
J
Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA. Jing_lin@groton.pfizer.com
Sahakian
Diana C
DC
de Morais
Sonia M F
SM
Xu
Jinghai J
JJ
Polzer
Robert J
RJ
Winter
Steven M
SM
D000042:Absorption; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D014018:Tissue Distribution