Pharmacokinetics of enteric-coated mycophenolate sodium: comparative study in patients with autoimmune disease and renal allograft

Abstract

Background: Recently, mycophenolic acid drugs have gained interest in the treatment of autoimmune diseases. However, only limited pharmacokinetic data are available on enteric-coated mycophenolate sodium in non-transplant indications. Objective: This study compared the pharmacokinetics of mycophenolic acid from enteric-coated mycophenolate sodium in patients with autoimmune disease and renal transplant recipients. Methods: Twelve autoimmune disease patients (mainly with antineutrophil cytoplasmic antibody-associated vasculitis) and 11 stable renal transplant patients, all of whom had been on enteric-coated mycophenolate sodium for ≥ 10 weeks, received an oral dose of enteric-coated mycophenolate sodium of 720 mg under fasting conditions. Blood samples for the determination of mycophenolic acid in the plasma were collected over 24 h. Results. Overall, no significant difference was found between both groups for their 0 – 12 h and 0 – 24 h areas under the concentration–time curve, Cmax, Tmax, C0 h, C12 h and C24 h, although the mean Cmax was numerically higher by 39% in the autoimmune disease patients (autoimmune disease 27.3 ± 17.4 mg/l and renal transplant 19.6 ± 15.7 mg/l). Patients on concomitant ciclosporin tended to have a lower mycophenolic acid exposure than patients on a non-ciclosporin regimen. The intersubject variabilities in the mycophenolic acid pharmacokinetics were high in both patient populations (around 40% for the area under the curve values). Both groups exhibited a weak and non-significant correlation between their mycophenolic acid trough (C12 h) levels and mycophenolic acid 0 – 12 h area under the curve (autoimmune disease r = 0.482 and renal transplant r = 0.138), whereas in the autoimmune disease group the mean C1.5 h and C2 h concentrations provided a satisfactory association with the 0 – 12 h area under the curve (for both r > 0.7 and p < 0.001). Conclusion: These data suggest that mycophenolic acid exposure (in terms of the area under the curve) from enteric-coated mycophenolate sodium is comparable in autoimmune disease and renal transplant patients. The mycophenolic acid trough levels did not reflect the systemic exposure to mycophenolic acid adequately; a limited sampling strategy for estimating mycophenolic acid exposure in autoimmune disease patients should include times around C1.5 h and/or C2 h reflecting Tmax if further studies confirm its usefulness.