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Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite
Authors:Kiehl M G  Shipkova M  Basara N  Blau I W  Schütz E  Armstrong V W  Oellerich M  Fauser A A
Affiliation:Department of BMT and Hematology/Oncology, Bone Marrow Transplant Unit, Dr. Ottmar-Kohler Str. 2, 55743, Idar-Oberstein, Germany. mkiehl@bmt-center-io.com
Abstract:OBJECTIVES: 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).CONCLUSION: MMF seems to be an effective treatment for aGvHD in SCT patients particular in those patients without gut involvement.
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