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

Service de Néphrologie-Immunologie Clinique, Hôpital Bretonneau, CHRU Tours, France melanie.roland{at}univ-tours.fr

C Barbet

Service de Néphrologie-Immunologie Clinique, Hôpital Bretonneau, CHRU Tours, France

G Paintaud

Service de Pharmacologie, Hôpital Bretonneau, CHRU Tours, France

C Magdelaine-Beuzelin

Service d’Immunologie, Hôpital Bretonneau, CHRU Tours, France

E Diot

Service de Médecine Interne, Hôpital Bretonneau, CHRU Tours, France

JM Halimi

Service de Néphrologie-Immunologie Clinique, Hôpital Bretonneau, CHRU Tours, France

Y Lebranchu

EA 4245 Université François Rabelais, Tours, France

H Nivet

EA 4245 Université François Rabelais, Tours, France

M Büchler

EA 4245 Université François Rabelais, Tours, France

Few 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 (T₀, 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 C₀ was 3.1 ± 2.2 mg/L. There was a high correlation between MPA AUC_0–4h and MPA C₀, (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 (<0.14 g/L). Moreover, there was a significant relationship between MPA trough levels and complement C4 concentrations (P = 0.043). We confirmed high inter-individual variability of MPA AUC in patients treated with MMF for SLE. This suggests that MPA exposure may be unpredictable with a fixed MMF dose. There was a concentration-effect relationship between MPA exposure (C₀) and immunological disease activity parameters.

Key Words: mycophenolate mofetil • pharmacokinetics • systemic lupus

Lupus, Vol. 18, No. 5, 441-447 (2009)
DOI: 10.1177/0961203308098631


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