Pharmacodynamics of tepoxalin, sodium-salicylate and ketoprofen in an intravenous lipopolysaccharide inflammation model in broiler chickens.
The pharmacodynamic properties of tepoxalin, Na-salicylate and ketoprofen were determined in an intravenous lipopolysaccharide (LPS) inflammation model in broiler chickens. The drugs were administered orally at a dose of 30, 50 and 3 mg/kg, respectively. LPS administration induces an increase in the intracellular expression of interleukin (IL)-1β and IL-6 and the secreted IL-6 plasma concentration. Furthermore, an elevation in body temperature is noted. Despite pretreatment with a single dose of the drugs and LPS administration on the T(max) of the drug after a second dose, no decrease was seen in systemic IL-6 levels. The intracellular expression of IL-1β in the heterophils was slightly decreased if LPS was administered in combination with each of the three drugs. Tepoxalin and Na-salicylate administration had no significant effect on the LPS-induced increase in prostaglandin E(2) plasma concentration, in contrast to ketoprofen. None of the three drugs were able to influence the elevation in body temperature after LPS administration. The pharmacokinetic properties of Na-salicylate and ketoprofen were not altered in combination with LPS administration. However, LPS significantly decreased the AUC(0→6 h) of the active metabolite of tepoxalin, RWJ-20142, indicating a perfusion-limited elimination for this molecule.
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. sandra.deboever@ugent.be
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de Boever
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Neirinckx
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Meyer
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de Baere
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Beyaert
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de Backer
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Croubels
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D002645:Chickens; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D015232:Dinoprostone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary*; D007275:Injections, Intravenous / Q000662:veterinary; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007660:Ketoprofen / Q000493:pharmacokinetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011201:Poultry Diseases / Q000188:drug therapy*; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D012980:Sodium Salicylate / Q000493:pharmacokinetics / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011720:Pyrazoles; D007660:Ketoprofen; D015232:Dinoprostone; C073135:tepoxalin; D012980:Sodium Salicylate