Detection, quantifications and pharmacokinetics of toltrazuril sulfone (Ponazuril®) in cattle

Toltrazuril sulfone (Ponazuril^®) is a triazine-based anti-protozoal agent with highly specific actions against apicomplexan group of organisms, which are undergoing intensive investigation. Toltrazuril sulfone may have clinical application in the treatment of Neospora. caninum and other protozoal infections in cattle. To evaluate absorption, distribution, and elimination characteristics of toltrazuril sulfone in cattle, a sensitive validated quantitative high-pressure liquid chromatography method for toltrazuril sulfone in bovine biological fluids was developed. After a single oral dose of toltrazuril sulfone at 5 mg/kg (as 150 mg/g of Marquis^®; Bayer HealthCare, Shawnee Mission, KS, USA), samples from six cows showed good plasma concentrations of toltrazuril sulfone, which peaked at 4821 ng/mL ± 916 (SD) at 48 h postadministration. Thereafter, plasma concentration declined to 1950 ng/mL ± 184 (SD) at 192 h after administration with an average plasma elimination half-life of ∼58 h. Following oral dose of toltrazuril sulfone, the observed peak plasma concentrations were in relatively close agreement ranging from the lowest 3925 ng/mL to the highest of 6285 ng/mL with the mean peak plasma concentration being 4821 ng/mL. This study shows that toltrazuril sulfone is relatively well absorbed after oral dose in cattle. These results are therefore entirely consistent with and support the reported clinical efficacy of toltrazuril sulfone in the treatment of experimentally induced clinical cases of N. caninum and other protozoal-mediated bovine diseases.     

Plasmid-mediated antibiotic resistance in Aeromonas salmonicida isolated from Atlantic salmon, Salmo salar L., in Scotland

Abstract. Forty oxytetracycline-resistant isolates of Aeromonas salmonicida obtained from outbreaks of furunculosis in Atlantic salmon in Scotland were tested for their susceptibility to 12 antibacterial agents. There were 10 resistance patterns with multiple resistance to two to six antibacterial agents. Transferable R-plasmids encoding oxytetracycline resistance were demonstrated in 11 out of the 40 isolates. The resistance transferred was multiple; to oxytetracycline, streptomycin, sulphamethoxine and trimethoprim, or to oxytetracycline and one or two of these in combination. Oxytetracycline resistance was transferred in a single, large step, >250-fold increase, and the MICs for individual transconjugants from mating populations were the same.     

Effect of oxidized fish oil, vitamin E and ethoxyquin on the histopathology and haematology of rainbow trout, Salmo gairdneri Richardson

Abstract. Rainbow trout were fed for 24 weeks on practical diets containing varying concentrations of oxidized fish oil, with or without supplementation of vitamin E and ethoxyquin. Serum biochemistry, haematology and histopathology were investigated to measure the relative protection offered by vitamin E (DL–α–toco–pherol acetate) and/or a synthetic substitute (ethoxyquin), against highly or extremely oxidized oil with peroxide values of 120 or 314mEq/kg oil respectively. Groups fed highly or extremely oxidized oils without DL–α–tocopherol acetate supplementation, and with or without supplemental ethoxyquin, exhibited lower red blood cell numbers, haemoglobin content, haematocrit, and increased haemolysis. In addition, fish from these groups had increased, abnormally developing polychromatocytes, splenic haemosiderosis and hepatic ceroidosis. The results indicate that vitamin E protects better and at lower concentrations than does ethoxyquin, and that supplementation with 33 mg of DL–α–tocopherol acetate/kg is adequate to prevent vitamin E deficiency signs when feeding practical diets containing 7.5 % of a highly oxidized oil. Supplementation with ethoxyquin alone to diets containing highly oxidized oil appeared to exert partial protection, but did not increase the level of protection when added simultaneously with DL–α–tocopherol acetate. The data support the theory of a general antioxidant function for vitamin E, and suggest that mortalities ensuing from vitamin E deficiency are due to the cumulative effects of liver dysfunction and anaemia.