Pharmacodynamics and pharmacokinetics of miloxicam in the horse.
The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/kg in a two-part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and lysozyme in inflammatory exudates harvested at 4, 8, 12 and 24 h were not significantly different in drug-treated animals compared with those receiving placebo. Concentrations of protein and lactate dehydrogenase (LDH) in exudate and exudate leucocyte numbers were significantly reduced in drug-treated horses when data for all sampling times were pooled. The differences were not significant, however, at each sampling time. Exudate concentrations of the eicosanoids, bicyclic-PGE2, 6-keto-PGF1 alpha and TXB2, were reduced significantly by miloxicam at most sampling times, and serum TXB2 was also significantly reduced at 4 and 8 h but not at 12 and 24 h after drug administration. These pharmacodynamic findings correlated with the pharmacokinetic properties of miloxicam. The plasma concentration-time curve was defined by a three-compartment open model in one pony and by a two-compartment model in five ponies. Mean values for pharmacokinetic parameters for the five ponies were: t1/2 alpha 0.40 h; t1/2 beta 2.70 h; Vd area 0.158 l/kg; ClB 41.87 ml/kg/h. Exudate concentrations of miloxicam were initially similar to and eventually greater than concentrations in plasma, and this may explain the more prolonged inhibition of eicosanoid synthesis in exudate than in serum. These findings demonstrate the value of relating, in a single experimental study, drug action on a range of variables to drug fate in the body.
Lees
P
P
Department of Veterinary Basic Sciences, Royal Veterinary College (University of London), Hertfordshire, UK.
Sedgwick
A D
AD
Higgins
A J
AJ
Pugh
K E
KE
Busch
U
U
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D000077239:Meloxicam; D013843:Thiazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013844:Thiazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam