Pharmacokinetics of mycophenolate mofetil in patients with autoimmune diseases compared renal transplant recipients.
Mycophenolate mofetil (MMF), being effectively used as immunosuppressant in transplant medicine, has recently attracted interest as therapeutic agent for autoimmune diseases (AID). For these patients, no pharmacokinetic (PK) data are available. This study is an investigation of single-dose concentration-time profiles of 1 g off MMF in 16 patients with AID, including 10 patients with ANCA-associated vasculitis and 6 patients with systemic lupus erythematosus, and compares them with profiles of 16 renal transplant recipients (RTX). Mycophenolic acid (MPA) blood levels were measured by both HPLC and EMIT, and MPA-glucuronide was determined by HPLC. In AID, mean MPA concentrations at 12 h were significantly higher compared with RTX (4.1 +/- 3.27 versus 1.8 +/- 1.15 mg/L; P = 0.018), whereas peak concentrations were lower (P = 0.017). However, mean MPA-AUC at 12 h as well as at 24 h were comparable between both groups. In contrast to RTX, there was an association in AID between MPA trough levels at 12 h and at 24 h with AUC(0-12) (P < 0.05 and P < 0.01). MPA trough concentrations at 24 h provided an estimation of AUC(0-24 h) in both patient groups (P < 0.001 and P < 0.01; AID and RTX, respectively). Compared with RTX, MPA-PK seems to be less affected in AID by renal function. Inter-individual variability of PK parameters was high in both groups. These data indicate that there are differences of MPA-PK between RTX and AID. The use of therapeutic drug monitoring in patients with AID appears to be clinically practicable and may be valuable to optimize individual immunosuppressive therapy.
Neumann
Irmgard
I
Department of Nephrology, Wilhelminenspital, Vienna, Austria. irmi_neumann@hotmail.com
Haidinger
Michael
M
Jäger
Heidemarie
H
Grützmacher
Hans
H
Griesmacher
Andrea
A
Müller
Mathias M
MM
Bayer
Peter M
PM
Meisl
Franz Thomas
FT
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D014657:Vasculitis / Q000188:drug therapy
D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid