kaolinite and Fever

The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 μg/mL and an IC(50) for R-ketoprofen of 1.6 μg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Female; Fever; Inflammation; Kaolin; Ketoprofen; Male; Models, Biological; Pain; Pain Measurement; Swine; Swine Diseases

The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Chromatography, Liquid; Drug Administration Schedule; Female; Fever; Inflammation; Injections, Intramuscular; Kaolin; Male; Meloxicam; Pain Measurement; Swine; Swine Diseases; Tandem Mass Spectrometry; Thiazines; Thiazoles

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Erythema; Female; Fever; Granuloma; Guinea Pigs; Hyperesthesia; Injections, Intravenous; Kaolin; Male; Mice; Peritonitis; Phenylbutazone; Pyrazoles; Rats; Terpenes; Ultraviolet Rays