Phmacodynamics and pharmacokinetics of carprofen, a non‐steroidal anti‐inflammatory 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 I/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 (xg/ml). In milk from mastitic quarters, concentrations of carprofen increased up to 0.164 Hg/ml during the first 12 h after induction of mastitis, but were less than 0.022 ug/ml at 24 to 48 h. Compared with the untreated mastitic controls, carprofen treatment significantly reduced 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.