Zhang B, Gu X, Li X, Gu M, Zhang N, Shen X, Li Y, Ding H
Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
J Vet Pharmacol Ther. 2014 Aug;37(4):367-73. doi: 10.1111/jvp.12100. Epub 2013 Dec 24.
A two-period cross-over study was carried to investigate the pharmacokinetics (PK) and ex-vivo pharmacodynamics (PD) of cefquinome when administrated intravenously (IV) and intramuscularly (IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC-MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two-compartment open model. Cefquinome mean values of area under concentration-time curve (AUC) were 5.15 μg · h/mL for IV dose and 4.59 μg · h/mL for IM dose. Distribution half-lives and elimination half-lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance (ClB ) and volume of distribution at steady-state (Vss ) were 0.49 L · kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 μg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 μg/mL in MHB and 0.032 and 0.064 μg/mL in serum. The ex vivo time-kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection.
进行了一项两阶段交叉研究，以调查头孢喹肟在7只健康犬体内静脉注射（IV）和肌肉注射（IM）2mg/kg体重剂量时的药代动力学（PK）和体外药效学（PD）。通过HPLC-MS/MS测定血清浓度，静脉注射和肌肉注射后头孢喹肟浓度与时间数据最适合二室开放模型。静脉注射剂量的头孢喹肟浓度-时间曲线下面积（AUC）平均值为5.15μg·h/mL，肌肉注射剂量为4.59μg·h/mL。静脉注射剂量和肌肉注射剂量后的分布半衰期和消除半衰期分别为0.27和0.44小时、1.53和1.94小时。总体清除率（ClB）和稳态分布容积（Vss）值分别为0.49L·kg/h和0.81L/kg。肌肉注射剂量后，Cmax为2.53μg/mL，生物利用度为89.13%。对于药效学曲线，在MHB中针对肺炎克雷伯菌测定的MIC和MBC值分别为0.030和0.060μg/mL，在血清中为0.032和0.064μg/mL。还在血清中建立了体外时间-杀菌曲线。结合MIC、MBC值和血清中体外杀菌活性的数据，目前的结果表明，2mg/kg的单一头孢喹肟剂量可能对犬肺炎克雷伯菌感染有效。
