Association of P450 Oxidoreductase Gene Polymorphism with Tacrolimus Pharmacokinetics in Renal Transplant Recipients: A Systematic Review and Meta-Analysis.

There are conflicting results regarding the effect of the P450 oxidoreductase () genotype on the tacrolimus (TAC) pharmacokinetics (PKs) during the early post-transplantation period in adult renal transplant recipients. Thus, we characterized the impact of on TAC PKs. We conducted a systematic review on the association between and PKs of TAC in adult renal transplant recipients. Structured searches were conducted using PubMed, Web of Science, and Embase. TAC standardized trough concentration (ng/mL per mg/kg) data were extracted. Mean differences (MD) and their corresponding 95% confidence intervals (CIs) were used to identify the differences between the genotype and PKs of TAC. The subgroup analysis was conducted according to expression status. Six studies (n = 1061) were included. TAC standardized trough concentrations were significantly lower in recipients with the allele compared to recipients with (MD: 8.30 ng/mL per mg/kg; 95% CI: 1.93, 14.67; = 0.01). In the subgroup analysis, TAC standardized trough concentrations were lower for subjects who were carriers than those who were in expressers (MD: 20.21 ng/mL per mg/kg; 95% CI: 16.85, 23.56; < 0.00001). No significant difference between carriers and was found in the non-expressers. The results of our meta-analysis demonstrated a definite correlation between the genotype and PKs of TAC. Patients carrying the allele may require a higher dose of TAC to achieve target levels compared to those with , especially in expressers.