Kyles Andrew E, Gregory Clare R, Craigmill Arthur L, Griffey Stephen M, Jackson Joshua, Stanley Scot D
Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA.
Am J Vet Res. 2003 Jul;64(7):926-34. doi: 10.2460/ajvr.2003.64.926.
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.
6 healthy research cats.
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.
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.
Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.
描述他克莫司在健康猫多剂量口服给药后的药代动力学，并评估他克莫司在预防肾移植猫同种异体移植排斥反应中的疗效。
6只健康的研究用猫。
猫接受他克莫司（0.375mg/kg，口服，每12小时一次），持续14天。通过高效液相色谱 - 质谱分析法测定血液中他克莫司的浓度。每只猫接受一个免疫原性不匹配的肾同种异体移植及自体肾切除术。调整他克莫司剂量以维持目标血药浓度在5至10ng/mL。如果血浆肌酐浓度超过7mg/dL、体重减轻超过20%或在术后第50天，则对猫实施安乐死。绘制了6只接受他克莫司治疗的猫和8只未接受免疫抑制治疗的肾移植猫的Kaplan-Meier生存曲线。
他克莫司最后一剂给药后至12小时的消除半衰期、达峰时间、最大血药浓度以及浓度 - 时间曲线下面积的平均值（±标准差）分别为20.5±9.8小时、0.77±0.37小时、27.5±31.8ng/mL和161±168小时×ng/mL。接受他克莫司治疗的猫比未治疗的猫存活时间更长（中位数为44天；范围为24至52天），未治疗的猫中位数为23天（范围为8至34天）。组织学评估显示，3只猫有急性活动性排斥反应的证据，1只猫有坏死性血管炎，在研究结束时实施安乐死的2只猫的同种异体移植肾外观正常。
他克莫司可能是猫肾移植有效的免疫抑制剂。
