Mycophenolic acid metabolite levels in pediatric liver transplantation: Correlation with a limited sampling strategy

Background: Although mycophenolate mofetil (MMF) has proven efficacy in preventing solid organ allograft rejection in adults, well-established dosing practices have yet to be established in children.This has led to the notion of developing therapeutic drug-monitoring techniques based on measuring the active mycophenolic acid (MPA) metabolite. Aim: The aim of this study is to establish an effective measure of plasma MPA metabolite levels based on a limited sampling strategy in pediatric liver transplant recipients. Plasma MPA levels were also correlated with conventional MMF dosing practices and concomitant immunosuppression. Methods: Plasma MPA metabolite levels were measured in 41 (23 female, 18 male) patients post (>7days) liver transplant from 2 major pediatric transplant centers by either a high performance liquid chromatographic or EMIT™ monitoring assay technique.The formal plasma MPA AUC was compared to an estimated MPA AUC by regression analysis. Results: Plasma MPA AUC_{(0-8 h)} metabolite levels correlated well with a limited sampling strategy based on the following equation: 9.1 + 5.7 x C₀ + 1.1 x C_{40 min} + 2.1 x C_2h (R = 0.74).There was a wide inter-patient variability in plasma MPA AUC metabolite levels despite conventional drug dosing practices. Patients on concomitant cyclosporine required higher mean (SEM) doses (548 [71] mg/day) of MMF compared to patients on tacrolimus (285 [71] mg/day) therapy (P < 0.02). Conclusion: Plasma MPA metabolites can be monitored in children post liver transplantation based on a limited sampling strategy. Future studies are needed to determine whether MMF therapy can be effectively tailored to improve overall clinical response based on the notion of therapeutic MPA metabolite monitoring.