Fosse T K, Toutain P L, Spadavecchia C, Haga H A, Horsberg T E, Ranheim B
Department of Food Safety and Infection Biology, The Norwegian School of Veterinary Science, Oslo, Norway.
J Vet Pharmacol Ther. 2011 Aug;34(4):338-49. doi: 10.1111/j.1365-2885.2010.01236.x. Epub 2010 Oct 11.
The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 μg/mL and an IC(50) for R-ketoprofen of 1.6 μg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.
在一项安慰剂对照研究中，对仔猪肌肉注射6 mg/kg消旋酮洛芬后的手性药代动力学和药效学进行了研究。两种对映体的吸收半衰期均较短，且血浆中S-酮洛芬的含量高于R-酮洛芬。采用高岭土诱导的炎症模型评估酮洛芬的抗炎、解热和镇痛作用。注射高岭土后皮肤温度升高，但酮洛芬的作用较小。未检测到明显的解热作用，但酮洛芬治疗的仔猪体温有降低趋势。采用机械性伤害性感受阈值测试评估镇痛效果。与安慰剂组仔猪相比，酮洛芬治疗组仔猪在治疗后12 - 24小时的机械性伤害性感受阈值显著更高。对机械性伤害性感受阈值测试结果进行药代动力学/药效学建模，得出S-酮洛芬的中位IC(50)为26.7 μg/mL，R-酮洛芬的IC(50)为1.6 μg/mL。这表明在仔猪中，R-酮洛芬比S-酮洛芬是一种更强效的镇痛药。消旋酮洛芬的估计ED(50)为2.5 mg/kg。
