Ketoprofen in piglets: enantioselective pharmacokinetics, pharmacodynamics and PK/PD modelling

Fosse, T.K.; Toutain, P.L.; Spadavecchia, C.; Haga, H.A.; Horsberg, T.E.; Ranheim, B. (2011). Ketoprofen in piglets: enantioselective pharmacokinetics, pharmacodynamics and PK/PD modelling. Journal of veterinary pharmacology and therapeutics, 34(4), pp. 338-49. Oxford: Blackwell Scientific Publications 10.1111/j.1365-2885.2010.01236.x

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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 mug/mL and an IC(50) for R-ketoprofen of 1.6 mug/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.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Spadavecchia, Claudia

ISSN:

0140-7783

Publisher:

Blackwell Scientific Publications

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:31

Last Modified:

21 Jan 2014 15:05

Publisher DOI:

10.1111/j.1365-2885.2010.01236.x

Web of Science ID:

000292464400004

URI:

https://boris.unibe.ch/id/eprint/12052 (FactScience: 218327)

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