Abstract

PHARMACOGENETICS OF DRUG METABOLISM AND TRANSPORT: CLINICAL IMPACT OF DRUG–GENE INTERACTIONS

Nimitt Prajapati, Dahima Param*, Bariya Bhumit Sinh, Ashok Kumar, Divyakant Patel

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Abstract

Background: Drug–gene interactions are a principal source of variability in medication response, often contributing to adverse drug reactions and treatment failures in clinical practice. Frequently implicated drug classes include nonsteroidal antiinflammatory drugs, diuretics, anticoagulants, and antiplatelet agents, with risk heightened by polypharmacy, particularly among the elderly. Genetic polymorphisms in key drugmetabolizing enzymes, notable CYP2C9, CYP2C19, and CYP2D6, account for significant variations in drug clearance and therapeutic outcomes. This review synthesizes recent literatures on drug–gene and drug–drug–gene interactions, focusing on pharmacokinetic and transporter-mediated mechanisms. It highlights the roles of enzyme inhibition, induction, and phenoconversion in altering pharmacological effects, and examines exemplars such as irbesartan, voriconazole, clopidogrel, and phenytoin. The analysis incorporates data from pharmacogenetics and transporter studies to elucidate underlying processes. Drug–gene interactions are involved in approximately 15% of all adverse drug reactions, while drug– drug–gene interactions account for an additional 19%. Clinical evidence demonstrates that patients with certain genotypes, like CYP2C9*3 alleles, exhibit marked changes in drug concentrations and responses. Moreover, transporter polymorphisms, although less extensively studied, significantly influence disposition of numerous therapeutics, further modifying efficacy and safety. Conclusion: Pharmacogenetics interactions between drugs and genes play a crucial role in individual responses to pharmacotherapy by modifying drug metabolism, elimination, and therapeutic efficacy. Although interactions involving transporters are less frequently examined, they are also significant in drug pharmacokinetics. In summary, a comprehensive understanding of pharmacogenetics is vital for enhancing drug treatment strategies and optimizing patient health outcomes.

Keywords: Pharmacogenetics, Phenoconversion, Drug–gene interactions, Drug transporters.