Assessing drug-drug interactions of Tacrolimus with Fluconazole and/or Verapamil and developing the predictive model for Tacrolimus concentrations in kidney transplant recipients

Abstract

Maintaining optimal tacrolimus serum concentrations is crucial for kidney transplant recipients due to its narrow therapeutic window and pharmacokinetic variability. The use of CYP3A4/5 inhibitors, such as fluconazole and verapamil, can increase tacrolimus serum concentrations. Understanding these interactions is vital for predicting and optimizing tacrolimus levels. This study aimed to investigate the impact of co-administering fluconazole, verapamil, or their combination on tacrolimus concentration/dose (C/D) in kidney transplant recipients and develop a predictive model for these scenarios. This retrospective study involved kidney transplant recipients treated with tacrolimus and co-administered fluconazole and/or verapamil. The Generalized Estimating Equations (GEE) approach was used to explore predictive variables associated with tacrolimus C/D. A total of 177 kidney transplant recipients were included. Repeated measure correlation analysis revealed positive correlations between tacrolimus C/D and dosages of fluconazole (b = 0.37, 95 % CI = 0.29 to 0.45, p < 0.001) and verapamil (b = 0.15, 95 % CI = 0.07 to 0.23, p < 0.001). This study offers a predictive model for optimizing tacrolimus levels when fluconazole and/or verapamil are co-administered in kidney transplant recipients.