A New Model to Determine Optimal Exposure to Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) After Renal Transplantation.

BACKGROUND: Drug dosing for TAC and MMF after kidney transplantation remains challenging. Therapeutic drug monitoring (TDM) offers a means to individualize drug dosing and improve outcomes. METHODS: In this observational study, patients having mycophenolic acid (MPA) exposure assessed by limited sampling strategy (LSS) within the first 6 months were included and followed for one year. RESULTS: 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 X (MPA AUC + MPAG/10 AUC) correctly classified outcomes. A score over 1,071 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. CONCLUSIONS: This integrated model of assessing TAC and MMF exposure may facilitate individualized therapy.