Abstract
Optimizing tacrolimus dosing is critical in renal transplantation to prevent acute rejection and minimize toxicity, yet significant inter-individual pharmacokinetic variability complicates management. This randomized controlled trial aimed to compare the efficacy and safety of pharmacogenomic-guided tacrolimus dosing, specifically leveraging CYP3A5 genotype, against a standard weight-based protocol in adult renal transplant recipients. Two hundred patients were randomized to either a pharmacogenomic-guided arm (initial dose adjusted based on CYP3A5 genotype) or a standard dosing arm. The primary endpoint was the time to achieve stable therapeutic tacrolimus trough levels (5-10 ng/mL). Secondary endpoints included the incidence of biopsy-proven acute rejection within the first six months, graft function, and adverse events. Results indicated that the pharmacogenomic-guided group achieved therapeutic tacrolimus levels significantly faster (median 3 days vs. 5 days, p < 0.001) and experienced a lower incidence of acute rejection (9% vs. 18%, p = 0.03). Graft function and adverse event rates were comparable between groups. These findings suggest that pharmacogenomic guidance based on CYP3A5 genotype offers a superior approach to early tacrolimus dosing, leading to more rapid therapeutic attainment and improved clinical outcomes in adult renal transplant recipients.
