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