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Anti-neutrophil cytoplasmic antibody-associated vasculitis ( AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid ( MPA) and the area under the curve ( AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA-AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique ( C0, C30, C1, C2, C3, C4, C6 and C9) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC0-12 was 50·55 (30·9-105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C3 ( P < 0·0001) and C2 ( P < 0·0001) and with C4 ( P < 0·0005) or C0 ( P < 0·001). Using linear regression, the best estimation of MPA AUC was provided by a model including C30, C2 and C4: AUC = 8·5 + 0·77 C30 + 4·0 C2 + 1·7 C4 ( P < 0·0001). Moreover, there was a significant relationship between MPA AUC0-12 and lymphocyte count ( P < 0·01), especially CD19 ( P < 0·005), CD8 ( P < 0·05) and CD56 ( P < 0·05). Our results confirm the interindividual variability of MPA AUC in patients treated with MMF in AAV and support a personalized therapy according to blood levels of MPA. [ABSTRACT FROM AUTHOR]

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, T30′, T1h, T2h, T3h and T4h) to determine the MPA AUC0-4h 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 AUC0-4h was 28.4 ± 13.6 mg h/L, mean dose-normalised AUC0-4h 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 MPAAUC0-4h and MPA C0, (r = 0.80;P < 0.001).AUC0-4h tended to be lower in patientswho 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. [ABSTRACT FROM AUTHOR]