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Tacrolimus (TAC) is the backbone of an immunosuppressive drug used in most solid organ transplant recipients. A single nucleotide polymorphism (SNP) at position 6986G>A in  CYP3A5  has been notably involved in the pharmacokinetic variability of TAC. It is hypothesized that  CYP3A5  genotyping in patients may provide a guideline for TAC therapeutic regimen. To further evaluate the impact of  CYP3A5  variants in donors and recipients,  ABCB1  and  ACE  SNPs in recipients on TAC disposition, clinical and laboratory data were retrospectively reviewed from 90 pediatric patients with liver transplantation and their corresponding donors after 1 year of transplantation. The recipients with  CYP3A5  *1/*1 or *1/*3 required more time to achieve TAC therapeutic range during the induction phase, and needed more upward dose during the late induction and the maintained phases, with lower C/D ratio, compared with those with  CYP3A5  *3/*3. And donor  CYP3A5  genotypes were found to impact on TAC trough concentrations after liver transplantation. No association between  ABCB1  or  ACE  genotypes and TAC disposition post-transplantation was found. These results strongly suggest that  CYP3A5  genotyping both in recipient and donor, not  ABCB1  or  ACE  is necessary for establishing a personalized TAC dosage regimen in pediatric liver transplant patients.

Personalized Tacrolimus Dose Requirement by CYP3A5 but Not ABCB1 or ACE Genotyping in Both Recipient and Donor after Pediatric Liver Transplantation