Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

Background

Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.

Methods

Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (F_rel) was determined for S and R –ketoprofen.

Results

S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.

Conclusions

Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.     

Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for treatment of cows with experimentally induced Escherichia coli mastitis

The efficacy of flunixin alone and together with enrofloxacin in treatment of experimental Escherichia coli mastitis was compared using six cows. The cross-over study design was used. Pharmacokinetics of flunixin and enrofloxacin were also studied in these diseased cows. The response of each cow was similar after the first and second challenge and the individual reaction seemed to explain the severity of clinical signs. The most important predictive factor for outcome of E. coli mastitis was a heavy drop in milk yield. Treatment with enrofloxacin and flunixin enhanced elimination of bacteria, but the difference from those receiving flunixin alone was not significant. Two cows, which had received no antimicrobial treatment (Group 1), were killed on day 4 postchallenge. One cow was killed after the first and the other after the second challenge. Cows receiving combination therapy produced 0.9 L more milk per day during the study period than cows which had only received flunixin (P < 0.05). Based on our findings, antimicrobial treatment might be beneficial in the treatment of high-yielding cows in early lactation. The absorption of enrofloxacin was delayed after subcutaneous administration, the mean apparent elimination half-life being about 23 h, whereas after i.v. administration elimination t(1/2) was only 1.5 h. The majority of the antimicrobial activity in milk originated from the active metabolite, ciprofloxacin, which could be measured throughout the 120-h follow-up period after the last subcutaneous administration. No differences were present in the pharmacokinetic parameters of flunixin between treatment groups: mean elimination half-life was 5.7-6.2 h, volume of distribution 0.43-0.49 L/kg and clearance 0.13-0.14 L h/kg. No flunixin or merely traces were detected in milk: one of the three cows had a concentration of 0.019 mg/L 8 h after administration.     

Over representation of Burmese cats with diabetes mellitus

Objective To determine if Burmese cats in Queensland have an increased risk of diabetes mellitus.
Design A retrospective study of diabetic and nondiabetic cats that had blood submitted to a veterinary clinical laboratory over a 22 month study period.
Sample population 4402 cats
Procedure Cats were considered diabetic if blood glucose concentration was > 11 mmol/L and fructosamine was > 406 μmol/L or hydroxybutyrate was >1 mmol/L. Cats were grouped into Burmese and non-Burmese. Adjusted odds ratios of diabetes were calculated for breed, gender and age group amongst cats with blood glucose > 11 mmol/L.
Results Burmese cats comprised 20% of 45 diabetic cats of known breed, which was higher (P < 0.001) than among the normoglycemic reference population of 2203 cats (7% Burmese). There were more females among the diabetic Burmese (62%), but this did not differ (P > 0.05) from the Burmese reference population (45% females). In contrast, males seemed to predominate among diabetic non-Burmese (63%), although this also did not differ (P > 0.05) from the reference population (55%) or from diabetic Burmese (38% males). The majority (90%) of diabetic cats were older than 6 years, irrespective of breed (median age 12 years, interquartile range 10 to 13 years). This was higher (χ²= 8.13, P < 0.005) than among the normoglycaemic reference population, where 69% were older than 6 years.
Conclusions Burmese cats were significantly over represented among cats with diabetes mellitus. Irrespective of breed, the risk of diabetes in the study population increased with age.