- Research Article
14
- 10.1111/jvp.12468
PK/PD modeling of flunixin meglumine in a kaolin-induced inflammation model in piglets.
- Nov 16, 2017
- Journal of Veterinary Pharmacology and Therapeutics
- O L Levionnois + 2 more +2
Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty-two piglets (6-8days 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, 10hr 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 50hr 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 4.4mg/kg showing the most relevant (6-10newton) and long-lasting effect (34hr). The median IC50 was 6.78 and 2.63mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin-induced inflammatory hyperalgesia in piglets.
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