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Pharmacokinetics of tacrolimus after multidose oral administration and efficacy in the prevention of allograft rejection in cats with renal transplants

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  • 1 Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.
  • | 2 Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.
  • | 3 School of Veterinary Medicine, and the Department of Environmental Toxicology, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.
  • | 4 Animal Resource Services, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.
  • | 5 Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.
  • | 6 Present address is 428 Rancho La Mirada Ln, Escondido, CA 92029.
  • | 7 Equine Analytical Chemistry Laboratory, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616.

Abstract

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, 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)

Abstract

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, 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)