Optimizing the dose of mycophenolate mofetil for the maintenance treatment of lupus nephritis by therapeutic drug monitoring

摘要

To evaluate the usefulness of monitoring the pharmacokinetic of mycophenolic acid (MPA) in lupus nephritis (LN), in order to optimize the mycophenolate mofetil (MMF) dose in the single patient. Five consecutive patients with active LN were studied. After standard induction therapy with MMF, MMF was titrated to achieve a stable target of MPA-AUC(0-12h) of 45-60 mg.h/l during the maintenance treatment. For MPA assays, blood samples were collected at 0, A1/2, 1 A1/4, 2, 4, 6, 8 and 12 h after the morning dose. Plasma MPA concentration was measured using a validated high-performance liquid chromatography. Treatment response was evaluated at baseline, i.e. at the end of the induction therapy and during maintenance therapy with MMF. The average whole follow-up was 21.4 months. At the last visit, a complete renal response was registered in all the five patients. No renal flares were observed. Glucocorticoids were suspended in all. The mean MPA-AUC(0-12h) of MMF at the last visit [56.74 (+/- 2.9) mg.h/l] was significantly lower than MPA-AUC(0-12h) at baseline [98.7 (+/- 24.6) mg.h/l] (p = 0.009), since the dose of MMF was significantly reduced in all the patients [from 2.8 g/day (+/- 0.4) to 1.9 g/day (+/- 0.4) (p = 0.018)] based on the target MPA-AUC. No severe adverse events were observed. Assessment of MPA pharmacokinetics may be useful to optimize the maintenance therapy of lupus nephritis with MMF, possibly improving the efficacy and minimizing the side effects.