Investigating genetic variations that influence drug metabolism and treatment outcomes

Original Article

Abstract

Background: Genetic differentiation influences variability in drug metabolism, clinical efficacy, and adverse reactions. Integrating genetic and epigenetic markers—such as cytochrome P450, thiopurine methyltransferase, and HLA variants—enhances pharmacogenomics precision and supports safer, more effective therapies.

Objective: To evaluate the pharmacogenomics correlates which define clinical outcome of administered medicine and correlating prescription of the individualized pharmacotherapy with guided genetic device. To determine their pharmacotherapeutic impacts and analyze if such genetic differences define clinical outcome and action.

Methods:This prospective study conducted in the Department of Pharmacology Khyber Medical college  Peshawar from jan 2023 to june 2023.100 adult patients. Genotyping CYP2D6, CYP2C19, and TPMT variants were done by using validated PCR-based assays. Pharmacokinetic parameters were measured by means of serial plasma sampling. Response to treatment and adverse events were recorded. The statistical analysis was done using T-test and chi-square tests with the adjustments of age, sex, and coeducations.

Results: The sample of 100 patients (mean age 54.2 +- 11.8 years) consisted of 28 poor metabolizers, 52 normal and 20 ultra-rapid metabolizers. The plasma drug concentration was better (p = 0.003) and adverse events were more common in poor metabolizers. Normal metabolizers showed a clinical response superior to that of poor metabolizers (p = 0.04). There were no significant differences in efficacy between ultra-rapid and normal metabolizers (p = 0.21) but a tendency toward lower plasma levels was evident. Genotype was determined to be a predictive independent variable in multivariate regression of pharmacokinetics and clinical outcome.

Conclusion: Genetic polymorphisms are significant in terms of pharmacokinetics, efficacy of therapy, and adverse effects. The net impact of the integration of pharmacokinetic testing into clinical practice may be improved dosing, reduced adverse event and improved patient outcome.. The wider use of personalized medicine strategies is justified to guarantee equal and efficacious healthcare services among the various types of patients.

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