Drug–drug interaction between tacrolimus and caspofungin in Chinese kidney transplant patients with different genotypes

Abstract

Background: The effect of drug–drug interaction between tacrolimus and caspofungin on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. Objectives: To investigate the effect of caspofungin on the blood concentration and dose of tacrolimus under different CYP3A5 genotypes. Design: We conducted a retrospective cohort study in The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital from January 2015 to December 2022. All kidney transplant patients were divided into the combination or non-combination group based on whether tacrolimus was combined with caspofungin or not. Patients were subdivided into CYP3A5 expressers ( CYP3A5*1/*1 or CYP3A5*1/*3 ) and CYP3A5 non-expressers ( CYP3A5*3/*3 ). Methods: Data from the combination and the non-combination groups were matched with propensity scores to reduce confounding by SPSS 22.0. A total of 200 kidney transplant patients receiving tacrolimus combined with caspofungin or not were enrolled in this study. Statistical analysis was conducted on the dose-corrected trough concentrations ( C 0 / D ) and dose requirements ( D ) of tacrolimus using independent sample two-sided t- test and nonparametric tests to investigate the impact on patients with different. Results: In this study, the C 0 / D values of tacrolimus were not significantly different between the combination and non-combination groups ( p = 0.054). For CYP3A5 expressers, there was no significant difference in tacrolimus C 0 / D or D values between the combination and non-combination groups ( p = 0.359; p = 0.851). In CYP3A5 nonexpressers, the C 0 / D values of tacrolimus were significantly lower in the combination than in the non-combination groups ( p = 0.039), and the required daily dose of tacrolimus was increased by 11.11% in the combination group. Conclusion: Co-administration of caspofungin reduced tacrolimus blood levels and elevated the required daily dose of tacrolimus. In CYP3A5 non-expressers, co-administration of caspofungin had a significant effect on tacrolimus C 0 / D values. An approximate 10% increase in the weight-adjusted daily dose of tacrolimus in CYP3A5 non-expressers is recommended to ensure the safety of tacrolimus administration.