Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf® or non-innovator formulations

TDM of tacrolimus is usually performed with trough levels (C-0h). However, in pediatric patients, C-0h may not be an adequate marker. The AUC is considered a more suitable indicator of drug exposure. As several blood samples are needed for the estimation of AUC, and LSS for predicting tacrolimus AUC and optimizing the dose adjustment have been proposed. Moreover, in emerging countries such as Mexico, non-innovator formulations, which bioequivalence has not been demonstrated, are frequently used. Hence, the aim of this study was to develop and validate a LSS to predict the tacrolimus AUC(0-12h) in Mexican pediatric kidney transplant recipients who received either Prograf (R) or non-innovator tacrolimus formulations. A total of 56 pharmacokinetic profiles were randomized into two groups: model development (n = 28) and model validation (n = 28). The limited sampling equations were obtained after a stepwise multiple regression using AUC as the dependent variable and tacrolimus blood concentrations, quantified by CMIA, at different time points as the independent variables. The final equation included observed concentrations at 1 hour (C-1h) and 4 hours (C-4h) after dose administration. The predictive performance of the model was adequate in terms of both, bias and precision. Results strongly suggest that the clinical use of this LSS could provide an ethical, cost-, and time-effective method in the TDM of tacrolimus in pediatric patients with kidney transplant. The model proved to be adequate with either Prograf (R) or non-innovator tacrolimus formulations of dubious bioequivalence.