Impact of glycaemic control and CYP3A5 polymorphisms on tacrolimus trough concentrations after adult kidney transplantation

Abstract

Aims: Diabetes mellitus affects the pharmacokinetics of cytochrome P450 3A4/5 (CYP3A4/5) substrates. We evaluated the relationship between haemoglobin A1c (HbA1c) levels and the pharmacokinetics of controlled-release tacrolimus. Methods: This retrospective observational cohort study included kidney transplant recipients (>18 years) receiving controlled-release tacrolimus orally. CYP3A5 genotypes were categorized as expressers (*1/*1 or *1/*3) and non-expressers (*3/*3). Multiple linear regression analysis determined the predictors for trough concentration/dose-normalized by body weight (C/D) ratio of tacrolimus at 7 days, 6 months and 12 months after administration. Correlations between the C/D ratio and HbA1c levels at baseline, 6 and 12 months after tacrolimus initiation were evaluated with Bonferroni correction. Results: Out of 42 patients (CYP3A5 expressers, n = 17, and non-expressers, n = 25), the multiple linear regression analysis showed that the C/D ratio on Day 7 was marginally higher in CYP3A5 non-expressers than in CYP3A5 expressers (r =.43, P =.028). Factors affecting the elevation of tacrolimus C/D ratio after 6 and 12 months of treatment were male sex and CYP3A5 non-expressers (r =.59, P