Pharmacokinetics of tacrolimus after multidose oral administration and efficacy in the prevention of allograft rejection in cats with renal transplants.
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.
Kyles
Andrew E
AE
Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA.
Gregory
Clare R
CR
Craigmill
Arthur L
AL
Griffey
Stephen M
SM
Jackson
Joshua
J
Stanley
Scot D
SD
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
D016559:Tacrolimus