ISSN:
1442-2042
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background A pharmacokinetic estimation of the immunosuppressive activity of mycophenolate mofetil (MPM) was performed in rats with transplanted kidney allografts. Methods Kidney allografts from Brown Norway rats were transplanted into Lewis rats using a microsurgical technique. MPM, at doses of 5, 10, 15 and 25mg/kg/day, was administered orally every day after transplantation. Pharmacokinetic studies were performed on days 7 and 14, and thereafter every 2 weeks. Results After the administration of MPM, the plasma concentration of mycophenolic acid (MPA) increased rapidly, peaking at 15 to 30 minutes, and then decreased biexponentially. The peak concentration of MPA and the area under the plasma MPA concentration versus time curves (AUC) significantly correlated with the dosage. MPM administration at 5 and 10mg/kg/day significantly prolonged the graft survival time from 7.1 days to 18.5 days and 85.0 days, respectively. The AUC values on day 7 after transplantation were 32.7,ug-h/mL and 38.6/ig-h/mL in rats receiving 5 and 10mg/kg/day, respectively. However, in rats receiving 1 5mg/kg/day of MPM or more, the AUC value at 7 days was 78.8,ug-h/mL, and almost all of these rats died from gastrointestinal toxicity. Conclusion MPM monotherapy significantly prolonged rat kidney allograft survival, however, high dosages of MPM caused gastrointestinal toxicity. AUC measurements of the MPA concentration are suitable for the pharmacokinetic monitoring of MPM.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1442-2042.1997.tb00189.x
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