Limited Sampling Strategies to Monitoring Mycophenolic Acid Exposure in a Heterogeneous Population of Heart Transplant Recipients: A Pilot Study

Abstract

Mycophenolate mofetil (MMF) represents a cornerstone in heart transplant (HTx) treatment. The area under the 12-hour concentration-time curve (AUC0-12h) of mycophenolic acid (MPA) -MMF’s active drug- is associated with treatment outcome. Nonetheless, therapeutic drug monitoring (TDM) of MPA AUC0-12h is impractical to assess in clinical practice and Limited Sampling Strategies (LSSs) represent a consolidated tool to estimate AUC0-12h. Two LSSs were previously generated in a selected cohort of HTx recipients treated with MMF and cyclosporine (CsA). This pilot study aimed to test these LSSs in a cohort of non-selected HTx recipients treated with MMF combined with CsA or tacrolimus (TAC). Complete PK profile was performed in 40 adults HTx recipients. MPA-AUC0-12h was estimated by two algorithms, LSS3 and LSS4, based on 3 and 4 time-points. The evaluation was made through linear regression and Bland-Altman analyses. Both LSS3 and LSS4 tended to underestimate the value of MPA-AUC0-12h (mean percentage prediction error, MPE%: −6.0%; and −4.8%, respectively). Nonetheless, high correlations (r: 0.92 and 0.94, respectively) and goodness of fit of linear regression models (R2: 0.84 and 0.88, respectively) emerged for both LSSs. A study with a wider and more homogenous sample size should be performed to support these results.