PK/PD modeling of flunixin meglumine in a kaolin-induced inflammation model in piglets

Levionnois, Olivier; Fosse, T. K.; Ranheim, B. (2018). PK/PD modeling of flunixin meglumine in a kaolin-induced inflammation model in piglets. Journal of veterinary pharmacology and therapeutics, 41(2), pp. 314-323. Blackwell Scientific Publications 10.1111/jvp.12468

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Anaesthesiology

UniBE Contributor:

Levionnois, Olivier

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0140-7783

Publisher:

Blackwell Scientific Publications

Language:

English

Submitter:

Helene Rohrbach

Date Deposited:

18 Apr 2018 11:12

Last Modified:

30 Oct 2019 19:13

Publisher DOI:

10.1111/jvp.12468

PubMed ID:

29143334

BORIS DOI:

10.7892/boris.109705

URI:

https://boris.unibe.ch/id/eprint/109705

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