Mycophenolate mofetil in patients with systemic lupus erythematosus: a prospective pharmacokinetic study

International audienceFew studies have assessed the pharmacokinetics of mycophenolic acid (MPA) in non-transplanted patients treated with mycophenolate mofetil (MMF), and little information is available concerning a concentration-effect relationship between the MPA area under the curve (AUC) and the immunological parameters in patients treated for systemic lupus erythematosus (SLE). We evaluated the variations in pharmacokinetics for MPA in patients with SLE and the relationship between MPA-AUC and markers of disease activity. MPA blood concentrations were measured through enzyme-multiplied immunotechnique (T(0), T(30'), T(1h), T(2h), T(3h) and T(4h)) to determine the MPA AUC(0-4h) in patients treated with MMF since at least 4 weeks for SLE. Clinical examination, biochemical analyses and immunological analyses were performed on the same day. The relationship between MPA exposure and disease activity markers was assessed. A total of 20 patients were included in the study. The diagnosis of SLE had been made 87 +/- 72 months before and patients had been treated with MMF for 31 +/- 30 months. Mean dose of MMF on the day of the study was 1600 +/- 447 mg/day. Mean MPA AUC(0-4h) was 28.4 +/- 13.6 mg h/L, mean dose-normalised AUC(0-4h) was 35.5 +/- 13.8 mg h/L and mean MPA C(0) was 3.1 +/- 2.2 mg/L. There was a high correlation between MPA AUC(0-4h) and MPA C(0), (r = 0.80; P < 0.001). AUC(0-4h) tended to be lower in patients who had low complement C3 concentration (<0.67 g/L) and low complement C4 concentration (