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健康奶牛和患乳腺炎奶牛中氟尼辛的药代动力学及乳汁消除比较。

Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis.

作者信息

Kissell Lindsey W, Leavens Teresa L, Baynes Ronald E, Riviere Jim E, Smith Geof W

机构信息

Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

出版信息

J Am Vet Med Assoc. 2015 Jan 1;246(1):118-25. doi: 10.2460/javma.246.1.118.

Abstract

OBJECTIVE

To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.

DESIGN

Prospective controlled clinical trial.

ANIMALS

20 lactating Holstein cows.

PROCEDURES

Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection.

RESULTS

For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.

CONCLUSIONS AND CLINICAL RELEVANCE

Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.

摘要

目的

确定健康奶牛和患乳腺炎奶牛在氟尼辛及5-羟基氟尼辛的药代动力学和乳汁消除方面是否存在差异。

设计

前瞻性对照临床试验。

动物

20头泌乳的荷斯坦奶牛。

步骤

患乳腺炎的奶牛和配对的对照奶牛静脉注射氟尼辛、肌肉注射头孢噻呋,并乳房内注射头孢匹林或头孢噻呋。在注射氟尼辛前(0时)以及注射后0.25、0.5、1、2、4、8、12、24和36小时采集血样。在0、2、12、24、36、48、60、72、84和96小时采集混合乳汁样本。血浆和乳汁样本采用超高效液相色谱-质谱检测法进行分析。

结果

对于血浆样本中的氟尼辛,检测到两组之间在浓度-时间曲线下面积和清除率方面存在差异。在不同时间点检测到乳汁中氟尼辛和5-羟基氟尼辛浓度存在差异。在氟尼辛给药后36小时(乳汁停药时间),8头患乳腺炎的奶牛5-羟基氟尼辛浓度高于耐受限度(即残留量)。10头患乳腺炎的奶牛中有3头在给药后60小时乳汁中仍有氟尼辛残留。

结论及临床意义

患乳腺炎奶牛和健康奶牛在氟尼辛及5-羟基氟尼辛的药代动力学和乳汁消除方面存在差异,导致出现违规残留。这可能部分解释了牛肉和奶牛中报道的大量氟尼辛残留情况。本研究还引发了关于在确定肉类和牛奶的停药时间时是否应使用健康动物的问题。

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