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 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 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, 275 ± 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 kad 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.