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. 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 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 AND CLINICAL RELEVANCE: Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.     

Tear-film osmolarity in normal cats and cats with conjunctivitis

Objective To compare the tear‐film osmolarity of normal cats and cats with conjunctivitis. Animal studied The population consisted of shelter, research, and privately owned cats. Procedures Cats were classified as normal or having conjunctivitis. An ophthalmic examination including Schirmer tear test (STT), fluorescein staining, tear‐film break‐up time (TFBUT), intraocular pressure (IOP), and slit‐lamp biomicroscopy of the anterior segment was performed. The severity of conjunctivitis was graded and assigned a numerical score. The Tear Lab^TM Osmolarity System was utilized to determine the tear‐film osmolarity. Unpaired t‐tests were used to compare tear‐film osmolarity, TFBUT, IOP, and STT of the two groups. Results A total of 93 cats (186 eyes) were examined. There were 37 normal cats (74 eyes) and 39 conjunctivitis cats (78 eyes). The mean age was 2.34 years. There was no statistical difference (P = 0.2065) between the median tear‐film osmolarity of normal cats (328.5 ± 17.94 mOsms/L) and conjunctivitis cats (325.0 ± 24.84 mOsms/L). Cats with conjunctivitis had an accelerated TFBUT (P < 0.0001) and lower IOPs (P < 0.0001) as compared to normal cats. No statistical difference was found between STT values (P = 0.1304). Conclusions The median tear‐film osmolarity of normal cats was 328.5 mOsms/L. Despite the accelerated TFBUT, conjunctivitis did not cause a statistically significant change in tear‐film osmolarity. The Tear Lab^TM Osmolarity System was easily used and well tolerated by the cats in the study.