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氟苯尼考在健康成年羊驼皮下和肌肉注射后的药代动力学

Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection.

作者信息

Holmes K, Bedenice D, Papich M G

机构信息

Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA 01536, USA.

出版信息

J Vet Pharmacol Ther. 2012 Aug;35(4):382-8. doi: 10.1111/j.1365-2885.2011.01323.x. Epub 2011 Jul 8.

Abstract

A single dose of florfenicol (Nuflor(®)) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross-over design, and 28-day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long-term effects. Maximum plasma florfenicol concentrations (C(max), measured via high-performance liquid chromatography) were achieved rapidly, leading to a higher C(max) of 4.31±3.03 μg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (C(max): 1.95±0.94 μg/mL). Multiple s.c. dosing at 48 h intervals achieved a C(max) of 4.48±1.28 μg/mL at steady state. The area under the curve and terminal elimination half-lives were 51.83±11.72 μg/mL·h and 17.59±11.69 h after single 2 mg/kg i.m. dose, as well as 99.78±23.58 μg/mL·h and 99.67±59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL, P<0.0001), globulin (2.76 vs. 2.16 g/dL, P<0.0003), albumin (3.61 vs. 3.48 g/dL, P=0.0038), white blood cell count (11.89 vs. 9.66×10(3)/μL, P<0.044), and hematocrit (27.25 vs. 24.88%, P<0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.

摘要

采用随机交叉设计,对8只健康成年羊驼分别以20mg/kg的剂量进行肌肉注射(i.m.)和40mg/kg的剂量进行皮下注射(s.c.),给予单剂量氟苯尼考(Nuflor(®)),洗脱期为28天。随后,每隔一天皮下注射40mg/kg氟苯尼考,共注射10次,以评估长期影响。通过高效液相色谱法测得的血浆氟苯尼考最大浓度(C(max))迅速达到峰值,肌肉注射20mg/kg后C(max)为4.31±3.03μg/mL,高于皮下注射40mg/kg后的C(max)(1.95±0.94μg/mL)。每隔48小时进行一次皮下多次给药,稳态时C(max)为4.48±1.28μg/mL。单次肌肉注射2mg/kg剂量后,曲线下面积和末端消除半衰期分别为51.83±11.72μg/mL·h和17.59±11.69小时,皮下注射40mg/kg氟苯尼考后分别为99.78±23.58μg/mL·h和99.67±59.89小时。在第0周和第3周重复给药后,氟苯尼考降低了以下血液学参数:总蛋白(6.38对5.61g/dL,P<0.0001)、球蛋白(2.76对2.16g/dL,P<0.0003)、白蛋白(3.61对3.48g/dL,P=0.0038)、白细胞计数(11.89对9.66×10(3)/μL,P<0.044)和血细胞比容(27.25对24.88%,P<0.0349)。在一只羊驼中观察到明显的临床疾病。因此,在羊驼中应使用最低有效剂量的氟苯尼考,并仅限于治疗高度易感病原体。

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