Individualized dosing of MMF is superior to fixed dosing in renal transplant patients
Original article
Le Meur Y et al. (2007) Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation. Am J Transplant 7: 2496–2503 PubMed
Mycophenolate mofetil (MMF) at a fixed dose of 2 g/day has been approved for the prevention of kidney allograft rejection in adults. The complex pharmacokinetics of MMF mean that actual exposure to the active metabolite of the drug (mycophenolic acid or MPA) can vary substantially between patients and in the same patient over time
Le Meur et al. recently developed an accurate model for determining MPA exposure. They have now applied this model during a 12-month, open-label, multicenter study.
Renal transplant recipients on an immunosuppressive regimen of basiliximab, ciclosporin (low target levels), gradual corticosteroid withdrawal and MMF were randomized to receive MMF at doses varied according to the Bayesian model or at fixed doses of 2 g/day (n = 65 in each group). The target for MPA exposure was 40 mg.h/l. Doses of MMF in the concentration-variable group were individualized at 7 days, 14 days, 1 month, 3 months and 6 months after transplantation.
After 1 year, significantly fewer patients in the group assigned to individualized MMF dosing had experienced treatment failure (a composite end point of death, graft loss, acute rejection and discontinuation of MMF; 29% vs 48%, P = 0.03). Variation in acute rejection rates accounted for the majority of this difference; 12% of patients in the concentration-variable group experienced an acute rejection episode, compared with 31% of those in the fixed-dose cohort. There were no differences in adverse event frequency between the two groups (>90% for both).
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Subject areas under which this article appears: Transplant
