Tacrolimus Dose Requirement Based On The CYP3A5Genotype In Renal Transplant Patients

BackgroundFor the kidney transplant patients, how to find the balance between the lowest drug given dose and the target blood concentrations and thus reduce the lowest chance for the toxicity and side effects could be happened to the patients is an important issue now. As known, the diversity of genes related to metabolic activity also affect the drug concentration.ObjectiveTo detect the CYP3A5genotype of the kidney transplant patients by PCR-SSP and determine CYP3A5*1and CYP3A5*3genotype could be the predictive index of tacrolimus dose requirement. MethodsWe tested archival peripheral blood of73kidney recipients for CYP3A5genotyping with PCR-SSP. We measured the dose-normalized blood concentrations of tacrolimus at1,3,6and12months after the renal transplantation, the frequency of rejection of different CYP3A5genotype, the influence on the hepatic and renal function of tacrolimus. ResultsThe frequency of CYP3A5*1/*1was6/73, CYP3A5*1/*3was23/73, and CYP3A5*3/*3was44/73.The CYP3A5*1carriers have a higher tacrolimus dose requirement than CYP3A5*3homozygote at1,3,6and12months after transplantation (P=0.0024). The CYP3A5*1carriers have a lower tacrolimus concentration than CYP3A5*3homozygote after transplantation,but there is no significant (P=0.6033).And CYP3A5*1was associated with significant lower tacrolimus dose adjusted concentration at1,3,6and12months after transplantation(P<0.0001). The carrier of CYP3A5*1have no significant difference with CYP3A5*3/*3on the frequency of rejection. Taking tacrolimus showed no significant effect on hepatic and renal function after transplantation.ConclusionsThese results indicate that CYP3A5*1carriers need higher tacrolimus dose than CYP3A5*3homozygote to achieve the target blood concentration. CYP3A5genotyping is a new approach for detecting tacrolimus dose requirement in kidney recipients.