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高效液相色谱法测定牛血浆中氟尼辛含量及单次和重复给药后的药代动力学

High-performance liquid chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug.

作者信息

Odensvik K, Johansson I M

机构信息

Department of Obstetrics and Gynaecology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.

出版信息

Am J Vet Res. 1995 Apr;56(4):489-95.

PMID:7785828
Abstract

A high-performance liquid chromatography method was developed for determination of flunixin in bovine plasma. The extraction procedure was easily performed and made it possible to detect low concentrations of flunixin with high accuracy. The limit of quantitation was 7 ng/ml (relative standard deviation = 18% n = 10). The analytic method permits processing of 60 samples/d. Flunixin, as well as the internal standard (diclofenac sodium), belong to the group of nonsteroidal anti-inflammatory drugs, which are known to have a high degree of binding to plasma proteins. Therefore, an evaluation of several buffer systems was undertaken to optimize analytic conditions. Cattle were given 2.2 mg of flunixin melgumine/kg of body weight. In experiment 1, single injections were administered IV to 1 cow and IV and IM to 1 heifer (7 days apart), and pharmacokinetic variables were calculated. The IV data were best described by a two-compartment model. The half-life after single IV or IM administration was around 4.0 hours. In experiment 2, the decreasing flunixin concentration was determined after the last of either 4 IM injections daily (n = 3 cows) or 2 IM injections daily (n = 3 cows) administered during a 14-day postpartum period. The half-life, determined between 48 and 96 hours after the last dose, was approximately 26 hours in both groups, and flunixin could be detected in plasma up to 8 days, on average. The protein binding of flunixin was studied, using the method of equilibrium dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

建立了一种高效液相色谱法用于测定牛血浆中的氟尼辛。该提取程序操作简便,能够高精度地检测低浓度的氟尼辛。定量限为7 ng/ml(相对标准偏差=18%,n=10)。该分析方法允许每天处理60个样品。氟尼辛以及内标(双氯芬酸钠)属于非甾体抗炎药组,已知它们与血浆蛋白有高度结合。因此,对几种缓冲系统进行了评估以优化分析条件。给牛按2.2 mg氟尼辛葡甲胺/千克体重给药。在实验1中,对1头母牛静脉注射,对1头小母牛静脉注射和肌肉注射(间隔7天),并计算药代动力学变量。静脉注射数据用二室模型描述最佳。单次静脉注射或肌肉注射后的半衰期约为4.0小时。在实验2中,测定了产后14天期间每天4次肌肉注射(n=3头母牛)或每天2次肌肉注射(n=3头母牛)最后一次注射后氟尼辛浓度的下降情况。在最后一剂后48至96小时测定的半衰期在两组中均约为26小时,平均而言,血浆中氟尼辛可持续检测8天。使用平衡透析法研究了氟尼辛的蛋白结合情况。(摘要截短至250字)

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