CYP3A41B but Not CYP3A53 as Determinant of Long-Term Tacrolimus Dose Requirements in Spanish Solid Organ Transplant Patients

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the allele (0.101 mg/kg; < 0.05). The results showed that patients with at least one allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of and variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies.