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

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 > or = 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, C(max), T(max), C(0 h), C(12 h) and C(24 h), although the mean C(max) 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 (C(12 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 C(1.5 h) and C(2 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 C(1.5 h) and/or C(2 h) reflecting T(max) if further studies confirm its usefulness.