The study on the efficacy, safety and pharmacokinetics of mycophenolate mofetil in pediatric renal transplantation

Abstract

 We conducted an open-label, single-arm multicenter study to evaluate the efficacy, safety and pharmacokinetics of MMF in Japanese pediatric renal allograft recipients, comparing with historical data in United Sates pediatric and Japanese adult renal allograft recipients. The primary efficacy outcome was the proportion of patients experiencing a biopsy-proven acute rejection episode within the first 6 months post-transplantation. Secondary efficacy outcomes were the proportion of patients who lost their graft by 12 months, the proportion of patients who died at 12 months.
 25 patients (2 to < 18 years) received MMF 300-600 mg/m² b.i.d. concomitantly with calcineurin inhibitor and corticosteroids with or without antilymphocyte antibody induction. Six patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) acute rejection episode within the first 6 months post-transplantation. One year after transplantation, patient and graft survival were 100% and 100%, respectively. Seventeen patients (68%) experienced adverse events. The most common adverse events related to MMF involved the infection associated with cytomegalovirus virus. Withdrawal of MMF due to adverse event was necessary in two patients. All adverse events associated with MMF were acceptable. The dosing regimen of MMF 300-600 mg/m² b.i.d. achieved the targeted in the first 3 months post-transplantation MPA 12-h area under concentration-time curve (AUC_0-12) of 48.7 ± 27.6 μg hr/ml. This was similar with AUC_0-12 of Japanese adult renal transplant recipients treated with MMF 2,000 mg b.i.d. The time course of estimated AUC_0-12 showed no clinically difference with that of United Sates pediatric renal allograft recipients treated with MMF 600mg/m² b.i.d.
 Administration of MMF 300-600mg/m² b.i.d. may be effective in prevention of acute rejection and be tolerant in Japanese pediatric renal transplant recipients, although this study has the limitation of study design and small patients' numbers. This dosing regimen provided predictable pharmacokinetics, too.