A new model to determine Optimal Exposure to Tacrolimus and Mycophenolate Mofetil after renal transplantation.

Abstract

Drug dosing for Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) after kidney transplantation remains challenging. Therapeutic drug monitoring (TDM) offers a means to individualize drug dosing and improve outcomes. In this observational study, patients having mycophenolic acid (MPA) exposure assessed by limited sampling strategy (LSS) within the first 6months were included and followed for 1year. A total of 113 clinical events occurring in 110 patients were classified into 3 groups: Group 1 Stable (n=34), Group 2 Over drug exposed (n=64) having infections or drug toxicity and Group 3 Under drug exposed (n=15) developing rejection or de novo donor-specific alloantibodies. Although TAC levels, MMF dose, MPA, and MPA Glucuronide (MPAG) exposure, expressed as area under curve (AUC), individually failed to predict outcomes, a scoring model incorporating all 3 drug levels TAC TDM×(MPA AUC+MPAG/10 AUC) correctly classified outcomes. A score over 1071 had a sensitivity and specificity of 0.94 (95% CI 0.56-0.83) and 0.84 (95% CI 0.69-0.89) for over exposure. A score below 625 had a sensitivity and specificity of 0.76 (95% CI 0.53-0.93) and 0.80 (95% CI 0.41-0.70) for under exposure. This integrated model of assessing TAC and MMF exposure may facilitate individualized therapy.