Evaluation of carprofen in calves using a tissue cage model of inflammation

被引:43
作者
Lees, P
Delatour, P
Foster, AP
Foot, R
Baggot, D
机构
[1] ECOLE NATL VET LYON,F-69280 MARCY LETOILE,FRANCE
[2] IRISH EQUINE CTR,JOHNSTOWN,KILDARE,IRELAND
来源
BRITISH VETERINARY JOURNAL | 1996年 / 152卷 / 02期
关键词
carprofen; enantiomers; calves; pharmacokinetics; pharmacodynamics;
D O I
10.1016/S0007-1935(96)80074-1
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg(-1) body weight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory and pharmacokinetic properties were investigated using a tissue cage model of inflammation based on intracaveal injection of the mild irritant, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring times. Elimination half-life and mean residence time were shorter and volume of distribution and clearance were greater for the S(+) than for the R(-) enantiomer. Penetration of both enantiomers into transudate (non-stimulated tissue cage) was poor but penetration into exudate (carrageenin-stimulated tissue cage) was good. Carprofen failed to reduce exudate concentration of prostaglandin E(2) and the reductions in 12-hydroxyeicosatetraenoic acid were non-significant at most sampling times. The long elimination half-life of both R(-) and S(+) carprofen enantiomers and their ready penetration into and slow clearance from inflammatory exudate indicate that the drug is likely to have a long duration of action in calves. The mechanism of action is unknown but it is unlikely to involve inhibition of either cycle-oxygenase or 12-lipoxygenase.
引用
收藏
页码:199 / 211
页数:13
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