Objective—To describe pharmacokinetics of multidose
oral administration of tacrolimus in healthy cats
and evaluate the efficacy of tacrolimus in the prevention
of allograft rejection in cats with renal transplants.
Animals—6 healthy research cats.
Procedure—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
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 × 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 and Clinical Relevance—Tacrolimus
may be an effective immunosuppressive agent for
renal transplantation in cats. (Am J Vet Res 2003;64:926–934)