title: Pharmacokinetics of tacrolimus after multidose oral administration and efficacy in the prevention of allograft rejection in cats with renal transplants.
abstract: OBJECTIVE
  To describe pharmacokinetics of multi-dose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants.
  
  
  METHODS
  6 healthy research cats.
  
  
  METHODS
  Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment.
  
  
  RESULTS
  Mean (+/- SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 +/- 9.8 hours, 0.77 +/- 0.37 hours, 27.5 +/- 31.8 ng/mL, and 161 +/- 168 hours x ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts.
  
  
  CONCLUSIONS
  Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.
authors.affiliation: Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Kyles
authors.forename: Clare R
authors.initials: CR
authors.lastname: Gregory
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Craigmill
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Griffey
authors.forename: Joshua
authors.initials: J
authors.lastname: Jackson
authors.forename: Scot D
authors.initials: SD
authors.lastname: Stanley
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002371:Cat Diseases / Q000601:surgery / Q000628:therapy*; D002415:Cats; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000662:veterinary*; D006207:Half-Life; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000662:veterinary*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D016559:Tacrolimus