PHARMACODYNAMICS AND PHARMACOKINETICS OF CARPROFEN, A NONSTEROIDAL ANTIINFLAMMATORY DRUG, IN HEALTHY COWS AND COWS WITH ESCHERICHIA-COLI ENDOTOXIN-INDUCED MASTITIS

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 < 0.01), and elimination half-life (43.0 h) was significantly longer (P < 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-mu-g/ml). In milk from mastitic quarters, concentrations of carprofen increased up to 0.164-mu-g/ml during the first 12 h after induction of mastitis, but were less than 0.022-mu-g/ml at 24 to 48 h. Compared with the untreated mastitic controls, carprofen treatment significantly reduced the heart rate (P < 0.01), rectal temperature (P < 0.001), quarter swelling (P < 0.01) and other parameters measured. Local and systemic adverse reactions to carprofen were not observed.