Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite.
OBJECTIVE
To investigate mycophenolate mofetil (MMF) plasma levels and impact on acute graft versus host disease (aGvHD) after stem cell transplantation (SCT).


METHODS
SCT patients (n = 14) with aGvHD (>/= II) receiving MMF (1-3 g/d) in addition to cyclosporine, prednisolone, and methotrexate for aGvHD prophylaxis were investigated. Plasma levels of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were determined by high-performance liquid chromatography.


RESULTS
Overall median steady state pre-dose plasma MPA concentration was 0.47 mg/L and increased within 75 min after administration to 1.64 mg/L. In comparison to patients with skin aGvHD, patients with gut aGvHD had lower MPA concentrations, both pre-dose (p = 0.16) and after 75 min, (p = 0.02). All 7 patients with skin aGvHD but only 2 patients with gut aGvHD responded to MMF. Overall, the pre-dose plasma MPA concentration was significantly (p = 0.007) greater in responders (n = 9) than in non-responders (n = 5).


CONCLUSIONS
MMF seems to be an effective treatment for aGvHD in SCT patients particular in those patients without gut involvement.
Kiehl
M G
MG
Department of BMT and Hematology/Oncology, Bone Marrow Transplant Unit, Dr. Ottmar-Kohler Str. 2, 55743, Idar-Oberstein, Germany. mkiehl@bmt-center-io.com
Shipkova
M
M
Basara
N
N
Blau
I W
IW
Schütz
E
E
Armstrong
V W
VW
Oellerich
M
M
Fauser
A A
AA
D004359:Drug Therapy, Combination; D005965:Glucuronates / Q000097:blood; D020719:Glucuronides; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000503:physiopathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use*; D011446:Prospective Studies; D014019:Tissue Donors
D005965:Glucuronates; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid