Heart Transplant Patients in a wide population observed for Mycophenolic Acid Area Under The Curve executed with a limited sampling strategy technique

Aim: The study aim is the validation of two algorithms of Limited Sampling Strategy (LSS) for the quantification of Mycophenolic Acid (MPA) Area under the plasma concentration-time curve from 0 to 12h (AUC0-12h) in a cohort of non-selected Heart Transplant (HTx) recipients treated, as standard clinical practice, with Mycophenolate Mofetil (MMF) combined with Cyclosporine (CsA), or Tacrolimus (TAC). These two LSSs were previously tested and validated by Baraldo et al. in a cohort of selected HTx recipients 1,2. The value of MPA AUC0-12h (real and estimated with LSSs) among non-rejected (NR) and rejected (R) patients were evaluated. Methods Linear regression and Bland Altman Analysis validated two LSSs methods (named LSS3 and LSS4 by number of blood samples used). The value of MPA AUC0-12h between NR and R patients were compared by Mann-Whitney test. Results The validation reports positive results for LSS3 and LSS4 according to linear regression (r=0.91 and 0.94 and R2=0.84 and 0.88, respectively) and Bland Altman Analysis (p=0.04 and 0.04). There was a difference of borderline statistically significance (p=0.06) for the median value of MPA AUC0-12h (mg×h/L) between NR and R patients (46.60; Interquartile Range (IQR): 34.80-64.10 vs 33.70; IQR: 23.60-48.25); whereas the difference was statistically significant for both LSS3 and LSS4 (p=0.03 and 0.04). Conclusion The capability of these two LSSs to estimate MPA AUC0-12h in cohort of non-selected HTx recipients and the suggestion of a significant difference on MPA AUC0-12h between NR and R patients, confirm the importance of MPA quantification in the clinical field.