Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy
OBJECTIVE To develop a population pharmacokinetic(PPK)model for mycophenolate mofetil active metabolite mycophenolic acid(MPA)in children with primary IgA nephropathy,explore the factors affecting the pharmacokinetic parameters of MPA,and provide a basis for clinical individualized therapy.METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy.PPK analysis was carried out by using the nonlinear mixed-effects model;the covariates were tested with a stepwise method.Goodness-of-fit plots,Bootstrap and visual predictive check were employed to evaluate the final model.RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model(objective function value of 3 276.31).Covariate analysis suggested that body weight and albumin(ALB)levels were significant influencing factors on apparent clearance rate and apparent distribution volume.The typical values of PPK parameters of MPA in the final model were as follows:the central room had a distributed volume of 5.79 L,the clearance rate was 4.06 L/h,the volume of peripheral ventricular distribution was 430.93 L,the clearance rate between compartments was 15.40 L/h,the oral absorption rate constant was 1.29 h-1.After verification,most of the predicted corrected observed concentration points were within the 90%confidence interval of the predicted corrected simulated concentration,indicating that the MPA final model had good predictive performance.CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study,identifying body weight and ALB levels are significant factors affecting MPA metabolism.
IgA nephropathymycophenolic acidchildrenpopulation pharmacokinetics
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