The pharmacokinetics of vedaprofen and its enantiomers in dogs after single and multiple dosing

Vedaprofen is a chiral nonsteroidal anti-inflammatory drug that has been developed as a gel formulation for oral administration to dogs and horses. The pharmacokinetics of vedaprofen and its enantiomers were studied in beagle dogs after single (intravenous solution and oral gel) and multiple (oral gel) dosing at a dosage of 0.5 mg/kg body weight. Plasma concentrations of vedaprofen and its enantiomers were analysed by HPLC. The plasma protein binding of vedaprofen was studied by ultrafiltration. The absorption of vedaprofen was rapid (tmax 0.63 +/- 0.14 h) and almost complete after oral administration (bioavailability 86 +/- 7%). The terminal half-lives after intravenous and oral administration, 16.8 +/- 2.2 and 12.7 +/- 1.7 h respectively, were of the same order of magnitude. Enantioselective analysis showed that the R(-) enantiomer predominated in plasma. The change in the plasma time course of the plasma R(-)/S(+) enantiomer concentration ratio over time was similar after single intravenous and oral dosing, with R(-)/S(+) ratios in the AUC of 1.7 +/- 0.5 and 1.9 +/- 0.2 respectively. Plasma protein binding of vedaprofen and its enantiomers was high (> 99.5%). Vedaprofen is absorbed rapidly from the gastrointestinal tract, has a high bioavailability and does not accumulate in plasma in dogs following repeated oral administration.     

Biochemical analysis of the articular cartilage and subchondral and trabecular bone of the metacarpophalangeal joint of horses with early osteoarthritis

OBJECTIVE: To assess whether site-related changes in biochemical composition are present in the cartilage and subchondral and trabecular bone of the metacarpophalangeal joint of horses with early osteoarthritis. SAMPLE POPULATION: Right metacarpophalangeal joints from 59 mature warmblood horses. PROCEDURE: Biochemical data (cross-link, amino acid, DNA, and ash contents; denatured collagen and glycosaminoglycan [GAG] concentrations; bone mineral density; and mineral composition) were obtained from 2 differently loaded sites of phalanx I cartilage and subchondral and trabecular bone samples; data were compared with previously published values from nonosteoarthritic equine joints. RESULTS: Compared with findings in nonosteoarthritic joints, GAG concentration was lower in cartilage from osteoarthritic joints and there was a loss of site differences in cellularity and lysylpyridinoline (LP) cross-link content. In subchondral bone, LP cross-link content was decreased overall and there was a loss of site differences in osteoarthritic joints; ash content was higher in the osteoarthritic joints. Hydroxyproline content in trabecular bone from osteoarthritic joints was greater than that in nonosteoarthritic trabecular bone. In all 3 layers and at both sites, the linear increase of the pentosidine cross-link content with age had diminished or was not apparent in the horses with osteoarthritic joints. CONCLUSIONS AND CLINICAL RELEVANCE: In equine metacarpophalangeal joints with early osteoarthritis, distinct biochemical changes were detected in the cartilage and subchondral and trabecular bone. The dissimilarity in response of the different tissues and differences between the sites that are affected may be related to differences in biomechanical loading and transmission and dissipation of force.     

Canine cyclic hematopoiesis: blood gas and 2,3-diphosphoglyceric acid studies

Cyclic hematopoiesis in gray Collies was first described in 1967. These dogs are anemic in comparison with the healthy littermates, and their erythropoiesis is abnormal. Although the basic disorder appears to be an as yet unidentified abnormality of hematopoietic progenitor cells, an inherent difference in responses to blood gas control mechanisms remains as a possible cause. In a study of these mechanisms in dogs with cyclic hematopoiesis, the P50 and 2,3-diphosphoglyceric acid concentrations were increased. Differences in pH, PCO2, PO2, and oxygen saturation were not observed.     

Influence of ambient temperature on prolactin concentrations in serum of Holstein and Brahman x Hereford heifers

Four Holstein and four Brahman x Hereford heifers about 8 mo of age were used in a study to determine whether breed influences the effects of ambient temperature on concentrations' of prolactin in serum. Two heifers of each breed were stanchioned in each of two environmental chambers at 21 C for 7 d, after which chamber temperatures were changed to 7 or 31 C during 6 h. After 5 d at 7, 21 or 31 C, heifers were injected with 60 micrograms thyrotropin-releasing hormone (TRH). A switch-back design was used and each heifer was exposed to all treatments. Concentrations of prolactin in serum of heifers during exposure to 7, 21 or 31 C for 5 d were related to ambient temperature (9.0, 20.9 and 29.5 ng/ml, respectively; P less than .001), but the response was not influenced by breed. Heifers of both breeds responded similarly to treatment with TRH, and prolactin in serum increased (P less than .001) within 5 min from 7.0 +/- 3.2 to 45.7 +/- 8.2 ng/ml in heifers at 7 C, from 13.1 +/- 1.6 to 97.2 +/- 9.6 ng/ml in heifers at 21 C and from 18.2 +/- 3.5 to 96.2 +/- 11.3 ng/ml in heifers at 31 C. We conclude that concentrations of prolactin in serum of heifers are positively associated with ambient temperature and that the effects of temperature on basal and TRH-stimulated concentrations of prolactin do not differ significantly between Holstein and Brahman x Hereford heifers. Thus, differences in tolerance to heat were not related to differences in prolactin secretion.     

EFFECT OF STRESS ON STEROID HORMONE LEVELS IN RACEHORSES

SUMMARY Cortisol and testosterone were measured by radioimmunoassay in plasma samples from race horses. None of 6 stressed male horses had Iow cortisol levels but testosterone levels (0.81 ± 0.15 nmol/l) were significantly lower than in healthy horses (1.86 ± 0.31 nmol/l). The conclusion was made that adrenocortical insufficiency is not a common association of stress in race horses. The reduction in testosterone levels is probably a nonspecific response similar to that seen in other species.     

Effects of grain type, roughage level and monensin level on finishing cattle performance

Interactions among grain type (grain sorghum, corn or wheat), roughage level and monensin level were studied in four feedlot trials using pen-fed crossbred yearling cattle. In Trial 1, cattle fed high-moisture corn (HMC) were more efficient (.1537 vs .1406 for gain/feed; P less than .01) than cattle fed dry-rolled grain sorghum (DRGS). As level (0, 3, 6, 9%) of dietary roughage was increased, feed efficiency (gain/feed) decreased (.1566, .1461, .1479, .1382; linear, P less than .01). In Trial 2, a grain type (DRGS; dry-rolled corn, DRC; dry-rolled wheat, DRW) x roughage level interaction was observed for daily gain and feed efficiency. Feed efficiency (gain/feed) was decreased when roughage was added to diets containing DRC (.1608 vs .1750) or DRGS (.1674 vs .1465), but not to the diet containing DRW (.1664 vs .1607). In trial 3, a grain type x roughage level x monensin level interaction (P less than .08) was observed for feed efficiency. The addition of 27.5 mg of monensin per kilogram of the 0% roughage-DRC diet tended to improve feed efficiency (.1633 vs .1531), but the addition of monensin to the 7.5% roughage-DRC diet tended to depress feed efficiency (.1476 vs .1575). The addition of either roughage (.1493 vs .1420) or monensin (.1500 vs .1413) to the DRW diet improved feed efficiency. In Trial 4, cattle fed a combination of 75% DRW and 25% DRC were more efficient (.1618 vs .1591; P less than .06) than cattle fed DRC. As level of roughage (0, 3.75, 7.5%) increased, feed efficiency decreased linearly (.1645, .1599, .1569; P less than .0001). Monensin had no effect on feed efficiency. The value of feeding roughage and monensin was variable both across grain types and within similar grain types.