Immunosuppression with FK778 and mycophenolate mofetil in a rat cardiac transplantation model
作者:
Tobias Deuse,
Sonja Schrepfer,
Hermann Reichenspurner,
期刊:
Transplantation
(OVID Available online 2003)
卷期:
Volume 76,
issue 11
页码: 1627-1629
ISSN:0041-1337
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
FK778 blocks the dihydro-orotate dehydrogenase, necessary for pyrimidine synthesis, and mycophenolate mofetil (MMF) inhibits the inosine monophosphate dehydrogenase, a crucial enzyme for purine biosynthesis. Beneficial immunosuppressive effects have been suggested for the combination of both drugs. The Brown Norway-Lewis rat heterotopic heart transplantation model was used. FK778 (5 and 20 mg/kg/day), MMF (10 and 40 mg/kg/day), or a combination of both drugs for 10 days was used for prevention of acute graft rejection. Grafts of untreated animals were rejected after 6.2±0.4 days. Low-dose FK778 and low-dose MMF administration did not result in a significantly prolonged graft survival (6.7±0.8 and 8.7±1.4 days;P=not significant). Grafts of rats treated with high-dose FK778 or high-dose MMF survived significantly longer (17.0±2.8 and 20.7±3.8 days;P<0.01). Concomitant use of low-dose FK778 with low-dose MMF produced synergistic interactions (mean survival time 12.3±2.9 days;P<0.01; combination index=0.85). High-dose drug combination (mean survival time 24.0±1.4 days) showed antagonistic drug interaction (combination index=1.55) with increased toxic side effects.
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