Limited sampling strategies (LSS) for estimating the area under the concentration time curve (AUC) of mycophenolic acid (MPA) in renal transplant children receiving concomitant tacrolimus have been developed, but not yet fully validated. The objectives of the present study were to evaluate the predictive performance of previously published LSS of MPA in an independent paediatric population, and validate a reliable and clinically applicable LSS for routine clinical practice. Published MPA LSS in renal transplant children were screened from the literature. MPA predicted AUCs were calculated using theses LSS, and were compared with the reference AUCs, which were calculated by the trapezoidal rule. External validation was prospectively performed in an independent validation group consisting of 44 renal transplant children. A total of 44 renal transplant children with a mean age of 12 years (range 3.45 - 20.57) and a mean weight of 35.8 kg (range 15.5 – 77.5) were included in the external validation dataset. The LSS2 equation: MPA-AUC0-12 = 12.6 + 7.78.C0 + 0.9.C1 + 1.3.C2 demonstrated a good predictive performance. Using this equation, the correlation between predicted and reference AUC was r2= 0.88; PE= 6.64; RMSE = 9.63 Bland altman = -1.36. The mean MPA- AUC0-12h obtained from LSS1 equation: MPA-AUC0-12 = 10.0 + 3.95×C0 + 3.24×C0.5 + 1.01×C2, MPA-AUC0-12h, and LSS2 were respectively; 65.23±33.84 µg.h/ml; 50.24±19.41 µg.h/ml; 51.75±19.41 µg.h/ml. The strength between full MPA-AUC0-12h and LSS2 obtained by Pearson correlation; r2 = 0.88 was higher than that with LSS1; r2 = 0.69. The linear regression value was superior with LSS2; R2 = 0.77 than that with LSS1; R2 = 0.472. The root mean square error (RMSE) was also inferior for David Netto method DNm ; RMSE = 9.63 than that obtained with of LSS1 RMSE = 28.82. The Bland-altman plot showed a bias of -1.36 for LSS2 and -14.99 for LSS1. A reliable and clinically applicable LSS was validated to predict MMF AUC in renal transplant children receiving concomitant tacrolimus and can be routinely used to adapted individual dose of MMF.

Keywords: Limited sampling strategy, mycophenolate mofetil, renal transplantation, children, tacrolimus.