Bioavailability and ADMET Parameters (Absorption, Distribution, Metabolism, Excretion, and Toxicity)

The failure of drug candidates in clinical trials is often due to poor pharmacokinetic profiles and toxicity, making the integration of ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation crucial in modern drug discovery (ADMET-by-Design). The fundamental concept is Bioavailability, defined as the fraction of a drug dose that reaches systemic circulation in unchanged form. Bioavailability is influenced by the solubility and permeability of molecules, which are evaluated early using empirical rules. Lipinski's Rule of Five establishes physicochemical criteria (such as MW