ADMET

ADMET — Absorption, Distribution, Metabolism, Excretion, and Toxicity — describes the pharmacokinetic and safety behaviour of a candidate compound within a...

ADMET — Absorption, Distribution, Metabolism, Excretion, and Toxicity — describes the pharmacokinetic and safety behaviour of a candidate compound within a living organism, and its early and continuous assessment throughout the discovery pipeline is essential because a substantial proportion of otherwise promising candidates fail not for lack of target potency but because of unfavourable ADMET properties. Absorption is influenced by aqueous solubility, membrane permeability, and susceptibility to efflux transport; distribution is governed by plasma protein binding and tissue partitioning; metabolism, predominantly mediated by cytochrome P450 enzymes, determines both systemic half-life and the risk of drug–drug interaction; excretion determines the ultimate elimination pathway and half-life; and toxicity encompasses both target-independent (off-target) and, less commonly, mechanism-based toxicity arising from the primary pharmacology itself. Early in-silico and in-vitro ADMET prediction, addressed in detail in Phase 1, allows unfavourable candidates to be deprioritised long before the expense of animal or human testing is incurred.