Background: The Area Under the Concentration-time curve (AUC) of Mycophenolic
Acid (MPA), is a valid prognosticator of the risk of rejection and the gold standard in its Therapeutic
Drug Monitoring (TDM), over time post-transplantation.
Objective: This study aimed to investigate MPA pharmacokinetic parameters and develop a Limited
Sampling Strategy (LSS) to estimate an abbreviated MPA AUC, in the stable phase post-renal
Methods: In this study, 19 patients with normal graft function (glomerular filtration rate >70
ml/min) who fulfilled the inclusion and exclusion criteria were involved. Blood samples at various
times were taken in the stable phase after transplantation. MPA plasma concentration was measured
by reverse-phase high-performance liquid chromatography. MPA AUC0–12h was calculated using
the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal
time points of MPA levels that could be used to yield model equations best fitted to MPA
AUC 0-12h. The findings of this study were compared with the results of our previous study, which
was done similarly in the early phase post-renal transplantation.
Results: The results demonstrated that the MPA-AUC and clearance were not affected over time,
but MPA-tmax was significantly lower in the stable phase in comparison with the early phase
(P=0.001). The best regression equation for AUC estimation in the stable phase was
AUC=9.57*C6+27.238 (r2=0.907). The validation of the method was performed using the jackknife
method. The mean prediction error of these models was not different from zero (P > 0.05) and had
a high root mean square prediction error (7.91).
Conclusion: In conclusion, the pharmacokinetics of MPA could be affected by time after transplantation,
making it essential to develop a limited sampling strategy as an efficacious approach for
therapeutic drug monitoring during the stable post-transplant period.