PHARMACOKINETIC CONSIDERATIONS IN DRUG DEVELOPMENT: A REVIEW
Keywords:
harmacokinetics, Drug Development, Absorption, Distribution, Metabolism, Excretion, Compartmental Models, Non-Compartmental Analysis, Physiologically-Based, Pharmacokinetic Models, Preclinical Studies, Clinical Trials, Pediatric Pharmacokinetics, Geriatric Pharmacokinetics, Renal Impairment, Hepatic Impairment, Drug Formulation, Controlled Release Systems, Regulatory Guidelines, Personalized Medicine, Pharmacogenomics.Abstract
Pharmacokinetics, the study of drug absorption, distribution, metabolism, and excretion (ADME), is crucial in the drug development process. This review provides an in-depth analysis of the fundamental concepts and parameters of pharmacokinetics, compartmental and noncompartmental models, and the integration of physiologically-based pharmacokinetic (PBPK) models. It explores preclinical pharmacokinetic studies, emphasizing in vitro and in vivo methodologies, predictive models for human pharmacokinetics, and ethical considerations. Clinical pharmacokinetic studies are discussed across various phases of clinical trials, highlighting dose escalation studies, drug-drug interaction assessments, and population pharmacokinetics. Special attention is given to pharmacokinetic variations in pediatric, geriatric, and renal or hepatic-impaired populations. The review also delves into pharmacokinetic considerations in drug design, covering oral, parenteral, and controlled release formulations, and the role of physicochemical properties, prodrugs, and bioconversion. Regulatory perspectives from the FDA, EMA, and ICH are outlined, focusing on the importance of pharmacokinetic data in the drug approval process and post-marketing surveillance. Finally, emerging technologies, the integration of pharmacokinetics and pharmacodynamics, and advancements in personalized medicine and pharmacogenomics are explored, highlighting future directions in the field. This comprehensive review underscores the pivotal role of pharmacokinetics in optimizing drug development and therapeutic outcomes.
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