Pypendop B H, Honkavaara J, Ilkiw J E
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
J Vet Pharmacol Ther. 2016 Oct;39(5):460-8. doi: 10.1111/jvp.12302. Epub 2016 Feb 20.
This study characterized the pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous bolus administration to cats. Seven 6- to-year-old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK-467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK-467 [75, 150, 300 or 600 μg/kg-only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two-compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half-life (min) were 342 (131-660), 829 (496-1243), 14.6 (9.6-22.7) and 48 (40-69) for D12.5; 296 (179-982), 1111 (908-2175), 18.2 (12.4-22.9) and 52 (40-76) for D25; 653 (392-927), 1595 (1094-1887), 22.7 (18.5-36.4) and 48 (35-60) for dexmedetomidine in D25M600; 117 (112-163), 491 (379-604), 3.0 (2.0-4.5) and 122 (99-139) for M300; and 147 (112-173), 462 (403-714), 2.8 (2.1-4.8) and 118 (97-172) for MK-467 in D25M600. MK-467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK-467.
本研究对右美托咪定、MK - 467及其组合静脉推注给药后在猫体内的药代动力学特征进行了表征。采用随机交叉设计，选用了7只6岁的雄性去势猫，体重为5.1±0.7千克。静脉注射右美托咪定[12.5（D12.5）和25（D25）微克/千克]、MK - 467[300微克/千克（M300）]或右美托咪定（25微克/千克）与MK - 467[75、150、300或600微克/千克 - 仅分析600微克/千克组（D25M600）的血浆浓度]，并在给药后8小时内采集血液。使用液相色谱/质谱法分析血浆药物浓度。二室模型最能拟合数据。D12.5组中央室的中位数（范围）体积（毫升/千克）、稳态分布容积（毫升/千克）、清除率（毫升·分钟/千克）和末端半衰期（分钟）分别为342（131 - 660）、829（496 - 1243）、14.6（9.6 - 22.7）和48（40 - 69）；D25组分别为296（179 - 982）、1111（908 - 2175）、18.2（12.4 - 22.9）和52（40 - 76）；D25M600组中右美托咪定的分别为653（392 - 927）、1595（1094 - 1887）、22.7（18.5 - 36.4）和48（35 - 60）；M300组分别为117（112 - 十六进制163）、491（379 - 604）、3.0（2.0 - 4.5）和122（99 - 139）；D25M600组中MK - 467的分别为147（112 - 173）、462（403 - 714）、2.8（2.1 - 4.8）和118（97 - 172）。MK - 467对右美托咪定的处置有中度但具有统计学意义的影响，而右美托咪定对MK - 467的处置影响极小。
