BIOAVAILABILITY AND ADMET PROFILE

Modern drug discovery and development is highly prone to failure, with inadequate ADMET profiles being the main cause of project termination in advanced clinical phases. Therefore, early evaluation of pharmacokinetic and toxicological properties has become crucial in the "fail fast, fail cheap" strategy. This review highlights the central role of Bioavailability—the fraction of unchanged drug reaching systemic circulation—as a prerequisite for efficacy. To predict good oral absorption, empirical rules such as Lipinski's Rule of Five and Veber's Rules focusing on Polar Surface Area and Rotatable Bonds are used as molecular design filters. ADMET is comprehensively evaluated: Absorption examines permeability and transporters; Distribution assesses plasma protein binding and penetration; Metabolism focuses on enzyme interactions predicting potential Drug-Drug Interactions; Excretion is determined by Clearance; and Toxicity evaluates risks of Cardiotoxicity and Hepatotoxicity. Integration of in silico predictions based on QSAR/QSPR models using platforms such as SwissADME, pkCSM, and ADMETlab enables medicinal chemists to perform rational optimization, significantly increasing success probability of new drug candidates.