Pharmacokinetics of kanamycin after subcutaneous and intravenous administration in dogs

Six beagle dogs were treated with kanamycin subcutaneously or intravenously in a dosage of 5 mg/kg. The plasma kanamycin concentration was measured over 24 hours by high pressure liquid chromatography with UV detection after derivatization and solid phase extraction. After subcutaneous application, kanamycin was absorbed quickly, and maximum plasma levels of 18.9 micrograms/ml in average after ca. 1 hour were measured. With complete systemic availability, the minimal inhibitory concentration of 4 micrograms/ml was maintained for 4 hours. After subcutaneous administration, kanamycin was terminally eliminated with a mean half life period of 2 hours.     

Pharmacokinetics of altrenogest in horses

The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentrations were measured by liquid chromatography-tandem mass spectrometry. The plasma levels of altrenogest reached maximal concentrations of 23-75 ng/mL. Baseline values were achieved within 3 days after the final administration. Urine peak concentrations of total altrenogest ranged from 823 to 3895 ng/mL. Twelve days after the final administration concentrations were below the limit of detection (ca 2 ng/mL).     

Reactivity of Equine Airways—A Study on Precision-cut Lung Slices

A study was performed to evaluate the use of precision-cut lung slices (PCLS) for studies on the contraction of equine airways. Lungs of 10 horses were taken to prepare PCLS of ˜250 μm from equine lung tissue using a special microtome. The lung slices were cultured and the enclosed small airways were monitored using a microscope with coupled digital camera, which was used to determine the airway luminal area and diameter from digital images. As indicated by the beating of the ciliated epithelium and reactivity of airways on methacholine challenge, the tissue slices were found to be viable for at least 24 h. The airways were not precontracted, as indicated by a missing dilatory effect of 1 mmol/L clenbuterol. Bronchoconstriction induced by both methacholine and histamine was found to be dose dependent. EC₅₀ values based on luminal area were 1.12 μmol/L · /÷ 3.82 for methacholine and 0.68 μmol/L · /÷ 6.99 for histamine. In conclusion, the PCLS technique is promising for studies on small airways in the equine lung. In the present study the basic principles of in vitro (ex vivo) examinations with equine PCLS on airway reactivity were developed.     

Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes

The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human atopic dermatitis. Their direct impact on keratinocytes, especially canine keratinocytes, is less obvious. Thus, an investigation was carried out to ascertain whether cyclosporin A and cilomilast modulate keratinocyte proliferation and secretion of proinflammatory mediators. Cyclosporin A inhibited canine and murine keratinocyte proliferation, whereas cilomilast had no affect. Cyclosporin A and cilomilast reduced the lipopolysaccharide-induced prostaglandin E2 synthesis in canine and murine keratinocytes. Both immunomodulators also inhibited the production of the CXC chemokine KC and CCL2 in the murine keratinocyte cell line MSC-P5. The two immunomodulators also significantly reduced the interferon-gamma-induced production of interferon-gamma-inducible protein 10 in human keratinocytes (HaCaT cells). Thus, cyclosporin A and cilomilast directly modulate keratinocyte functions which might contribute to the anti-inflammatory and immunomodulatory action of these compounds in the treatment of allergic skin diseases.     

Quantitative analysis of tylosin in eggs by high performance liquid chromatography with electrospray ionization tandem mass spectrometry: residue depletion kinetics after administration via feed and drinking water in laying hens

Maximum residue limits (MRLs) have been established by the European Union when tylosin is used therapeutically. They are fixed at 200 microg/kg for eggs. A highly sensitive and selective quantitative liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method suitable for monitoring tylosin residues in eggs to determine its depletion kinetics was developed and validated. For sample pretreatment all samples were liquid-liquid extracted with citrate buffer (pH 5.0) and acetonitrile. Liquid chromatographic separation was carried out on a reversed phase C18 column employing a 0.5% formic acid/acetonitrile gradient system. The tylosin recovery in eggs at a concentration range from 1.0-400 microg/kg was >82% with relative standard deviations between 1.5 and 11.0%. In two experimental studies administrating tylosin via feed (final dosage: 1.5 g/kg) or drinking water (final dosage: 0.5 g/L), no residues above the MRL were found during and after treatment. Moreover, all samples were well below the actual MRL of 200 microg/kg. Therefore, our residue data suggest that a withholding period for eggs is not required when laying hens are treated with tylosin in recommended dosages via feed or drinking water. Keywords: Tylosin; residue; depletion; laying hen; withholding period; mass spectrometry.     

Tissue distribution of cefquinome after intramammary and "systemic" administration in the isolated perfused bovine udder

Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. Cefquinome (88.8mg cefquinome sulphate per 8mL) was administered by the intramammary route to all quarters and/or "systemically" via the perfusion fluid at concentrations similar to those measured in plasma following intramuscular administration of 1mg cefquinome per kg body weight. Samples of the perfusate were taken over a 6-h period and from the regional lymph nodes after 6h. Using a scalpel, sections of glandular tissue - at different distances from and vertical to the teat right up to the udder base - were gathered from four quarters each per route of administration at 2, 4 and 6h. The cefquinome content of the tissue samples was analysed by high performance liquid chromatography with diode array detection and of the perfusate samples by bioassay. After intramammary administration, the concentration of cefquinome in the glandular tissue decreased exponentially with increasing distance from the teat. The addition of cefquinome to the perfusion fluid produced a mean concentration of 0.2-0.5microg/g at all glandular tissue sites. Combined intramammary and systemic treatment ensured that concentrations exceeded the MIC(90) values of the most common mastitis pathogens in all areas of the udder by 2h post-administration. There was considerable variability in the tissue concentrations of cefquinome, particularly after intramammary administration. These results suggest that for the treatment of acute mastitis a combination of both intramammary and systemic administration is likely to be advantageous in order to rapidly produce maximum cefquinome concentrations in all regions of the udder.