title: ADDME--Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective.
abstract: The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity.
authors.affiliation: Apredica, 313 Pleasant Street, Watertown, MA 02472, USA. Katya@Apredica.com
authors.forename: Katya
authors.initials: K
authors.lastname: Tsaioun
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.forename: Aloise
authors.initials: A
authors.lastname: Mabondzo
mesh_terms: D001692:Biological Transport; D001812:Blood-Brain Barrier; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008928:Mitochondria
chemical_list: D002491:Central Nervous System Agents