EFFECT OF GENOTYPE- AND THERAPEUTIC DRUG MONITORING-GUIDED TACROLIMUS DOSING IN RENAL TRANSPLANT RECIPIENTS WITH EXTENSIVE METABOLISM

Abstract

Objectives: The aim of this study was to evaluate the effect of genotype- and therapeutic drug monitoring (TDM)-guided tacrolimus dosing in renal transplant recipients with extensive metabolism. Methods: This prospective observational study included 34 renal transplant recipients identified as extensive metabolizers from a cohort of 210 patients. Tacrolimus dosing was guided by genotype and optimized using TDM over a 12-month follow-up period. Tacrolimus pharmacokinetic parameters, renal function, and immunological biomarkers (Interleukin [IL]-2, CD3, CD4, and CD8) were assessed. Peak tacrolimus concentration at 1.5 h post-dose (C1.5h) was also evaluated. Results: The mean observed tacrolimus dose was significantly lower than the predicted dose for extensive metabolizers (6.01±1.43 mg vs. 7.43±1.09 mg; p<0.001), dose/weight ratio decreased significantly during follow-up (p<0.001), while tacrolimus trough concentrations remained stable. Serum creatinine levels showed a significant reduction (p=0.016), indicating preserved graft function. A statistically non-significant weak positive correlation was observed between tacrolimus trough concentration and IL-2, CD3, and CD4 levels, whereas a statistically non-significant weak negative correlation was noted with CD8 levels. Eight patients exhibited peak tacrolimus concentrations >20 ng/mL, and five showed C1.5h/D ratios >4 ng/mg. Conclusion: Genotype-and TDM-guided tacrolimus dosing was associated with a significant reduction in dose requirements while maintaining immunological markers within the expected range. However, these findings should be interpreted with caution due to the single-arm observational study design. Monitoring peak concentrations may complement trough-based monitoring and help identify patients at risk of excessive tacrolimus exposure.