PK/PD modeling of flunixin meglumine in a kaolin‐induced inflammation model in piglets. Issue 2 (16th November 2017)

• Record Type: Journal Article
• Authors: Levionnois, O. L.; Fosse, T. K.; Ranheim, B.
• Is Part Of: Journal of veterinary pharmacology and therapeutics. Volume 41:Issue 2(2018)
• Page Start: 314
• Page End: 323
• Publication Date: 2017-11-16
• Subjects: Veterinary pharmacology -- Periodicals; Therapeutics -- Periodicals; 636.0895105
• DOI: 10.1111/jvp.12468
• Languages: English
• ISSNs: 0140-7783

Abstract

Abstract : 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.