The use of intradermal carrageenan in calves to estimate the dose of oxindanac, a nonsteroidal anti-inflammatory drug.
A simple and humane model of inflammation, induced by the intradermal injection of 0.3 mL of sterile 2% carrageenan, was characterized in calves by measuring the volume of skin swelling plus histological analysis of skin biopsies. Carrageenan produced a biphasic increase in skin swelling, with an early edematous response followed by a more chronic cellular infiltrate. The swelling and sensitivity to pressure observed in the early response were suitable for testing the antiedematous and analgesic activity of a new nonsteroidal anti-inflammatory drug (NSAID), oxindanac. Pretreatment with intravenous oxindanac at doses from 0.5 to 8.0 mg/kg reduced the volume of swelling and this reached statistical significance (p < 0.05) at 2 mg/kg. The ED50 and ED90 values for inhibition of the peak swelling volume (4 h) were estimated to be 1 mg/kg and 2 mg/kg, respectively. These compare with an ED90 of 2.0 mg/kg for inhibition of serum TxB2 production, an index of platelet cyclo-oxygenase activity. The dose of oxindanac required for antiedematous activity correlated, therefore, with maximal inhibition of serum TxB2. The analgesic activity of oxindanac reached no clear maximum response, but statistically significant difference (p < 0.05) from placebo was reached with doses of 2 mg/kg and above. It is concluded that intradermal carrageenan produced a simple, humane and useful model for dose estimation of a new NSAID in calves.
King
J N
JN
Ciba-Geigy Animal Health, Centre de Recherches Agricoles, St Aubin, Switzerland.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002351:Carrageenan / Q000008:administration & dosage; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007192:Indenes / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary*; D007271:Injections, Intradermal / Q000662:veterinary; D008297:Male; D011312:Pressure; D012867:Skin / Q000473:pathology; D013929:Thromboxane B2 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007192:Indenes; D013929:Thromboxane B2; D002351:Carrageenan; C039724:oxindanac