Determination of pharmacokinetics and pharmacodynamics of flunixin in calves by use of pharmacokinetic/pharmacodynamic modeling.
Pharmacokinetic and pharmacodynamic variables of flunixin were studied in calves after IV administration of the drug at a dose rate of 2.2 mg/kg of body weight. The anti-inflammatory properties of flunixin were investigated, using a model of acute inflammation; this involved surgically implanting tissue cages at subcutaneous sites and stimulating the tissue cage granulation tissue by intracavitary injection of carrageenan. The actions of flunixin on exudate concentrations of several substances related to the inflammatory process, including proteases (metalloprotease [active and total] and cysteine and serine proteases), enzymes (lactate dehydrogenase, acid phosphatase, and beta-glucuronidase [beta-glu]), eicosanoid (prostaglandin E2 [PGE2], leukotriene B4, and serum thromboxane B2 [TXB2]) concentrations, and bradykinin (BK)-induced edema, were investigated. Flunixin had a long elimination half-life--6.87 +/- 0.49 hours--and volume of distribution was 2.11 +/- 0.37 L/kg, indicating extensive distribution of the drug in the body. Body clearance was 0.20 +/- 0.03 L/kg/h. Flunixin exerted inhibitory effects on serum TXB2 and exudate PGE2 concentrations, beta-glu activity, and BK-induced swelling. Other enzymes and inflammatory mediators were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Landoni
M F
MF
Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, Hatfield Herts, United Kingdom.
Cunningham
F M
FM
Lees
P
P
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002417:Cattle; D003002:Clonixin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018592:Cross-Over Studies; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005122:Exudates and Transudates; D005966:Glucuronidase / Q000032:analysis; D007249:Inflammation / Q000188:drug therapy; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008657:Metabolic Clearance Rate; D008666:Metalloendopeptidases / Q000378:metabolism; D008954:Models, Biological; D012697:Serine Endopeptidases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C014557:flunixin; D007770:L-Lactate Dehydrogenase; D000135:Acid Phosphatase; D005966:Glucuronidase; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases; D003002:Clonixin