title: 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 > 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).
  
  
  CONCLUSIONS
  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.
authors: Wilhelminenspital, Department of Nephrology, Montleartstreet 37, A-1171 Vienna, Austria. irmgard.neumann@wienkav.at
authors: Irmgard
authors: I
authors: Neumann
authors: Heinz
authors: H
authors: Fuhrmann
authors: Marina
authors: M
authors: Kanzler
authors: I-Fei
authors: IF
authors: Fang
authors: Adelheid
authors: A
authors: Jaeger
authors: Helmut
authors: H
authors: Graf
authors: Peter
authors: P
authors: Bayer
authors: Josef
authors: J
authors: Kovarik
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013608:Tablets, Enteric-Coated
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid