Evaluation of carprofen in calves using a tissue cage model of inflammation.
The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 body weight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory and pharmacokinetic properties were investigated using a tissue cage model of inflammation based on intracaveal injection of the mild irritant, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring times. Elimination half-life and mean residence time were shorter and volume of distribution and clearance were greater for the S(+) than for the R(-) enantiomer. Penetration of both enantiomers into transudate (non-stimulated tissue cage) was poor but penetration into exudate (carrageenin-stimulated tissue cage) was good. Carprofen failed to reduce exudate concentration of prostaglandin E2 and the reductions in 12-hydroxyeicosatetraenoic acid were non-significant at most sampling times. The long elimination half-life of both R(-) and S(+) carprofen enantiomers and their ready penetration into and slow clearance from inflammatory exudate indicate that the drug is likely to have a long duration of action in calves. The mechanism of action is unknown but it is unlikely to involve inhibition of either cyclooxygenase or 12-lipoxygenase.
Lees
P
P
Department of Veterinary Basic Sciences, Royal Veterinary College, Hatfield, Hertfordshire, UK.
Delatour
P
P
Foster
A P
AP
Foot
R
R
Baggot
D
D
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002351:Carrageenan; D002417:Cattle; D002418:Cattle Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D015232:Dinoprostone / Q000032:analysis; D005122:Exudates and Transudates / Q000737:chemistry / Q000187:drug effects*; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D008297:Male; D011506:Proteins / Q000032:analysis; D013997:Time Factors; D015054:Zymosan / Q000008:administration & dosage
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D006893:Hydroxyeicosatetraenoic Acids; D011506:Proteins; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002351:Carrageenan; D015054:Zymosan; C007005:carprofen; D015232:Dinoprostone