Validation of an abbreviated pharmacokinetic profile for the estimation of mycophenolic acid exposure in pediatric renal transplant recipients.

The pharmacokinetics of mycophenolic acid (MPA), the active moiety of the immunosuppressant mycophenolate mofetil (MMF), exhibits large inter-individual variability. Concentration-controlled dosing of MMF based on therapeutic drug monitoring may therefore be advantageous compared to a fixed-dose regimen. Because full AUC(0-12) monitoring is not practical and predose MPA concentrations correlate only moderately with the corresponding AUC(0-12), the estimation of MPA exposure by a limited sampling strategy has been suggested. However, before such an algorithm is transferred to clinical practice, it is compulsory to prospectively validate it in a different data set, in order to avoid biased results. The aim of this investigation was therefore to prospectively validate an algorithm based on an abbreviated pharmacokinetic (PK) profile for the estimation of MPA exposure in 54 pediatric renal transplant recipients (169 PK profiles) on MMF in conjunction with CsA and prednisone on a second data set in a different group of patients with a similar immunosuppressive regimen (25 patients, 119 PK profiles). An algorithm based on three PK sampling timepoints during the first 2 hours after MMF dosing (estimated AUC(0-12) = 18.6 + 4.3 x C(0) + 0.54 x C(0.5) + 2.15 x C(2)) was able to predict the corresponding MPA-AUC(0-12) with a low percentage prediction error (10.7%) and an acceptable coefficient of determination (r = 0.76). The performance of this algorithm was comparable among different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC(0-12) based on this algorithm was able to differentiate between rejecters and non-rejecters with a comparable prognostic sensitivity (66.7%) and specificity (61.9%) as the full-time MPA-AUC(0-12). In conclusion, the use of this validated algorithm for the estimation of MPA exposure based on a limited sampling strategy during the first 2 hours after MMF dosing has the potential to optimize MMF therapy in pediatric renal transplant recipients.