title: Pharmacokinetic studies of mycophenolate mofetil in rat kidney allograft recipients.
abstract: 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 25 mg/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 10 mg/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 micrograms.h/mL and 38.6 micrograms.h/mL in rats receiving 5 and 10 mg/kg/day, respectively. However, in rats receiving 15 mg/kg/day of MPM or more, the AUC value at 7 days was 78.8 micrograms.h/mL, and almost all of these rats died from gastrointestinal toxicity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: N
authors.initials: N
authors.lastname: Sugioka
authors.forename: K
authors.initials: K
authors.lastname: Hayashida
authors.forename: T
authors.initials: T
authors.lastname: Yasumura
mesh_terms: D000818:Animals; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid