Pharmacokinetics and Drug Disposition: The Role of Physiological and Biochemical Factors in Drug Absorption and Elimination

Abstract

The understanding of Pharmacokinetics and drug disposition (absorbed, distributed, metabolized, and excreted (ADME)) Of drugs within human system is of critical importance to understand active mode of action. The dependence of the drug’s bioavailability, therapeutic efficacy, and potential toxicity on these processes is well known. Among these various factors, enzyme activity, transport proteins, organ function, and genetic variations affecting factors involved in absorption and elimination of drugs can play a decisive role. Knowing these factors makes drug dosing more optimized and less adverse effects. The variable nature of drug disposition is dominated by a number of factors including age, sex, genetic polymorphisms, comorbidities and environmental factors. It is critical that from drug plasma levels are kept within the therapeutic window and avoid toxicity through the interaction between drug metabolism and excretion pathways. Liver and kidney are the major organs in which a drug is eliminated, however, when the function of either of them is impaired, pharmacokinetic parameters can be significantly changed causing drug accumulation or even reduced efficacy.

Furthermore, pharmacokinetic modeling as well as recent development in precision medicine has helped personalize therapeutic treatments in the way that drug therapy outcomes can be improved by considering the inter-individual variability. This review articles presents a comprehensive review of the principles of drug pharmacokinetics which governs drug disposition and the physiological and biochemical factors that are governing absorption and elimination of drugs. It also discusses the evolution of trends in drug metabolism and excretion and identifies the future trends in designing drugs in order to improve delivery of drug and minimize adverse reactions.