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氟苯尼考在猪静脉注射和肌肉注射后的贝叶斯群体药代动力学建模

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration.

作者信息

Liu Zhichang, Rong Ting, Zeng Dongping, Shen Xiangguang, Ma Xianyong, Zeng Zhenling

机构信息

Key Laboratory of Animal Nutrition and Feed Science (South China) of Ministry of Agriculture, State Key Laboratory of Livestock and Poultry Breeding, Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China.

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

出版信息

J Vet Pharmacol Ther. 2018 Oct;41(5):719-725. doi: 10.1111/jvp.12677. Epub 2018 Jul 5.

Abstract

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two-compartment open model with the typical values of half-life at α phase (t ), half-life at β phase (t ), total body clearance (Cl), and volume of distribution (V ) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg , respectively. The disposition of florfenicol after i.m. administration was best described by a one-compartment open model. The typical values of maximum concentration of drug in serum (C ), elimination half-life (t ), Cl, and Volume (V) were 5.52 ± 0.605 μg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr  kg , and 3.28 ± 0.402 L/kg, respectively. The between-subject variabilities of all the parameters after i.m. administration were between 25.1%-92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. administration.

摘要

基于健康猪只静脉注射(i.v.)或肌肉注射(i.m.)后的回顾性数据,建立了氟苯尼考在健康猪体内的贝叶斯群体药代动力学模型。静脉注射后,氟苯尼考的处置过程最好用二室开放模型来描述,α相半衰期(t)、β相半衰期(t)、总体清除率(Cl)和分布容积(V)的典型值分别为0.132±0.0289、2.78±0.166小时、0.215±0.0102和0.841±0.0289L/kg。肌肉注射后氟苯尼考的处置过程最好用一室开放模型来描述。血清中药物最大浓度(C)、消除半衰期(t)、Cl和容积(V)的典型值分别为5.52±0.605μg/ml、9.96±1.12小时、0.228±0.0154L·hr/kg和3.28±0.402L/kg。肌肉注射后所有参数的个体间变异性在25.1%-92.1%之间。肌肉注射后氟苯尼考吸收良好(94.1%)。根据蒙特卡洛模拟,静脉注射和肌肉注射后,8.5和6mg/kg足以对胸膜肺炎放线杆菌发挥90%的杀菌作用。

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