Levionnois O L, Fosse T K, Ranheim B
Veterinary Anaesthesiology and Pain therapy, Vetsuisse Fakultat Universitat Bern, Bern, Switzerland.
Voss, Norway.
J Vet Pharmacol Ther. 2018 Apr;41(2):314-323. doi: 10.1111/jvp.12468. Epub 2017 Nov 16.
Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty-two piglets (6-8 days old) were randomized to receive placebo saline (n = 11, group CONTROL) or flunixin meglumine intravenously at 2.2 (n = 11, group MEDIUM) or 4.4 (n = 10, group HIGH) mg/kg, 10 hr after subcutaneous injection of kaolin in the left metacarpal area. A hand-held algometer was used to determine each piglet's mechanical nociceptive threshold (MNT) from both front feet up to 50 hr after treatment (cut-off value of 24.5 newton). Serial venous blood samples were obtained to quantify flunixin in plasma using LC-MS/MS. A PKPD model describing the effect of flunixin on the mechanical nociceptive threshold was obtained based on an inhibitory indirect response model. A two-compartmental PK model was used. A significant effect of flunixin was observed for both doses compared to control group, with 4.4 mg/kg showing the most relevant (6-10 newton) and long-lasting effect (34 hr). The median IC50 was 6.78 and 2.63 mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6 mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin-induced inflammatory hyperalgesia in piglets.
氟尼辛在多个国家作为成年猪的镇痛药上市，但对其在仔猪中的疗效了解甚少。32头仔猪（6 - 8日龄）被随机分为三组，分别静脉注射安慰剂生理盐水（n = 11，对照组）、2.2 mg/kg氟尼辛葡甲胺（n = 11，中等剂量组）或4.4 mg/kg氟尼辛葡甲胺（n = 10，高剂量组），在左掌骨区域皮下注射高岭土10小时后给药。使用手持式痛觉计在治疗后长达50小时测定每头仔猪两只前脚的机械性伤害感受阈值（MNT）（截止值为24.5牛顿）。采集系列静脉血样，采用液相色谱 - 串联质谱法（LC - MS/MS）定量血浆中的氟尼辛。基于抑制性间接反应模型获得了描述氟尼辛对机械性伤害感受阈值影响的药代动力学 - 药效学（PKPD）模型。使用了二室药代动力学模型。与对照组相比，两个剂量的氟尼辛均观察到显著效果，4.4 mg/kg组显示出最显著（6 - 10牛顿）且持久（34小时）的效果。中等剂量组和高剂量组的半数抑制浓度（IC50）中位数分别为6.78和2.63 mg/ml。该模型中的半数有效剂量（ED50）为6.6 mg/kg。氟尼辛对仔猪高岭土诱导的炎性痛觉过敏表现出显著的镇痛作用。
