Pharmacology of ketoprofen administered orally to pigs: an experimental and clinical study
Year: 2012
Type: dissertation
Abstract: Ketoprofen is a non-steroidal anti-inflammatory drug belonging to the 2-arylpropionic acid group. It has been widely used in domestic animals because of its anti-inflammatory, antipyretic and analgesic actions. Ketoprofen is a chiral compound existing in two enantiomeric forms, S (+) and R (-) ketoprofen. Each enantiomer has different pharmacodynamic and pharmacokinetic properties. The commercial products in veterinary medicine are 50:50 racemic mixtures of both enantiomers. Ketoprofen undergoes unidirectional chiral inversion from the R- to the S-enantiomer, the extent of inversion being about 70% in pigs. The aims of this thesis research were to investigate the oral bioavailability, enantiospecific plasma concentrations and efficacy of racemic ketoprofen after oral administration in pigs. Total plasma concentrations of ketoprofen were investigated in a randomized crossover design. Racemic ketoprofen was administered at 3 mg/kg and 6 mg/kg po, and 3 mg/kg im and iv. The bioavailability of oral ketoprofen was almost complete. Bioequivalence could not be detected between oral and intramuscular administration routes. Plasma concentrations of S- and R-ketoprofen after oral (4 mg/kg) and intramuscular (3 mg/kg) routes of administration of racemic ketoprofen in pigs were determined in crossover design. S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The maximum plasma concentration of S-ketoprofen was more than twice as high as that of R-ketoprofen, and the terminal half-life was approximately three times greater for S-ketoprofen than R-ketoprofen with both administration routes. The mean (± SD) relative bioavailability (po compared to im) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively. Although some differences were detected in the plasma concentrations of ketoprofen enantiomers after different routes of administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen are considered to be comparable after intramuscular and oral routes of administration in growing pigs. The efficacy of orally administered racemic ketoprofen in endotoxemia in pigs was assessed in an E. coli endotoxin challenge trial. The growing pigs were challenged intravenously with E. coli endotoxin and one hour after the challenge were treated with ketoprofen at dose rates of 0.5 mg/kg, 1 mg/kg, 2 mg/kg and 4 mg/kg or with tap water. The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B2 and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered the blood thromboxane B2 concentrations when compared to the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. Two mg/kg can be considered a sufficient oral dose of ketoprofen for treating endotoxemia in pigs, as increasing the dose above this did not further increase the effect. Lameness is a common problem among sows and gilts. It often leads to poor animal welfare and economic losses because of unplanned culling. Locomotor disorders cause severe pain, and lame animals need to be treated accordingly. A field trial was conducted to examine the efficacy and compare two doses of oral administration of racemic ketoprofen in the treatment of clinical lameness caused by non-infectious musculoskeletal disorders in sows and gilts. Dose rates of 2 mg/kg and 4 mg/kg of oral ketoprofen were compared to placebo treatment over five consecutive days in a double-blinded study. Lameness was assessed with a five-grade scoring system prior to and on the last day of the treatment. This study demonstrated that oral ketoprofen was efficient in alleviating the signs of non-infectious lameness in sows and gilts. The rate of treatment success was 54.3% for the ketoprofen 4 mg/kg group, 53.2% for the ketoprofen 2 mg/kg group and 20.8% for the pigs in the placebo group. There was no difference in efficacy between the two ketoprofen doses. Oral ketoprofen appeared to be a practical way to alleviate pain and improve the welfare of lame sows. The findings support the use of ketoprofen at a dose rate of 2 mg/kg in treating locomotor disorders in pigs.
Source: Työväentutkimus Vuosikirja
Author: Katja Mustonen
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1936903846