title: Pharmacodynamics and pharmacokinetics of carprofen, a non-steroidal anti-inflammatory drug, in healthy cows and cows with Escherichia coli endotoxin-induced mastitis.
abstract: The pharmacodynamics of carprofen and its pharmacokinetics in plasma and milk of healthy cows and cows with endotoxin-induced mastitis were studied after a single intravenous dose of 0.7 mg/kg body weight. Carprofen was administered to five clinically healthy cows and to the same cows 3 weeks later, 2 h after intramammary infusion of endotoxin. Mastitis developed in all endotoxin-infused quarters. The pharmacokinetic characteristics of carprofen in healthy cows were a small volume of distribution (0.09 l/kg), a relatively low systemic clearance (2.4 ml/h kg), and a long elimination half-life (30.7 h). In the mastitic cows, systemic clearance (1.4 ml/h kg) was significantly lower (P less than 0.01), and elimination half-life (43.0 h) was significantly longer (P less than 0.01) than in the normal animals. Concentrations of carprofen in milk from healthy quarters were below the limit of detection for the assay (0.022 micrograms/ml). In milk from mastitic quarters, concentrations of carprofen increased up to 0.164 micrograms/ml during the first 12 h after induction of mastitis, but were less than 0.022 micrograms/ml at 24 to 48 h. Compared with the untreated mastitic controls, carprofen treatment significantly reduced heart rate (P less than 0.01), rectal temperature (P less than 0.001), quarter swelling (P less than 0.01) and other parameters measured. Local and systemic adverse reactions to carprofen were not observed.
authors.affiliation: Department of Herd Health and Reproduction, College of Veterinary Medicine, State University of Utrecht, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Lohuis
authors.forename: T
authors.initials: T
authors.lastname: van Werven
authors.forename: A
authors.initials: A
authors.lastname: Brand
authors.forename: A S
authors.initials: AS
authors.lastname: van Miert
authors.forename: E
authors.initials: E
authors.lastname: Rohde
authors.forename: B
authors.initials: B
authors.lastname: Ludwig
authors.forename: P
authors.initials: P
authors.lastname: Heizmann
authors.forename: W F
authors.initials: WF
authors.lastname: Rehm
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001831:Body Temperature; D002227:Carbazoles / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002417:Cattle / Q000378:metabolism*; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D007774:Lactation; D008070:Lipopolysaccharides; D008414:Mastitis, Bovine / Q000188:drug therapy / Q000378:metabolism*; D008892:Milk / Q000032:analysis / Q000166:cytology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; C007005:carprofen