Mycophenolate mofetil in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a prospective pharmacokinetics and clinical study

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 (C-0,C- C-30, C-1, C-2, C-3, C-4, C-6 and C-9) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC(0-12) was 50 center dot 55 (30 center dot 9-105 center dot 4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C-3 (P < 0 center dot 0001) and C-2 (P < 0 center dot 0001) and with C-4 (P < 0 center dot 0005) or C-0 (P < 0 center dot 001). Using linear regression, the best estimation of MPA AUC was provided by a model including C-30, C-2 and C-4: AUC = 8 center dot 5 + 0 center dot 77 C-30 + 4 center dot 0 C-2 + 1 center dot 7 C-4 (P < 0 center dot 0001). Moreover, there was a significant relationship between MPA AUC(0-12) and lymphocyte count (P < 0 center dot 01), especially CD19 (P < 0 center dot 005), CD8 (P < 0 center dot 05) and CD56 (P < 0 center dot 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.