Faecal excretion profile of moxidectin and ivermectin after oral administration in horses

A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days post-treatment. After faecal drug extraction and derivatization, samples were analysed by High Performance Liquid Chromatography using fluorescence detection and computerized kinetic analysis.For both drugs the maximum concentration level was reached at 2.5 days post administration. The ivermectin treatment groups' faecal concentrations remained above the detectable level for 40 days (0.6 +/- 0.3 ng/g), whereas the moxidectin treatment group remained above the detectable level for 75 days (4.3 +/- 2.8 ng/g). Ivermectin presented a faster elimination rate than moxidectin, reaching 90% of the total drug excreted in faeces at four days post-treatment, whereas moxidectin reached similar levels at eight days post-treatment. No significant differences were observed for the values of maximum faecal concentration (C(max)) and time of C(max)(T(max)) between both groups of horses, demonstrating similar patterns of drug transference from plasma to the gastrointestinal tract. The values of the area under the faecal concentration time curve were slightly higher in the moxidectin treatment group (7104 +/- 2277 ng.day/g) but were not significantly different from those obtained in the ivermectin treatment group (5642 +/- 1122 ng.day/g). The results demonstrate that although a 100% higher dose level of moxidectin was used, attaining higher plasma concentration levels and more prolonged excretion and gut secretion than ivermectin, the concentration in faeces only represented 44.3+/- 18.0% of the total parental drug administered compared to 74.3 +/- 20.2% for ivermectin. This suggests a higher level of metabolization for moxidectin in the horse.     

Hepatic cirrhosis in a five-month-old dog

The clinicopathological features of an unusual case of a five-month-old male Spanish mastiff, which was presented with clinical signs indicative of severe hepatic failure, are reported. Fluid replacement therapy, colloid plasma expanders, antibiotics and diuretic drugs were unsuccessful in improving the animal's general condition, and euthanasia was elected by the owner. On necropsy, ascites and severe cirrhosis, with extensive periacinar necrosis, was found. Cirrhosis is a rare lesion in young dogs. The most common causes are circulatory disturbances, hereditary metabolic disorders or poisoning, such as aflatoxicosis and anticonvulsant therapy. The possible involvement of canine adenovirus in this case is discussed.     

Absorption of inorganic, trivalent and hexavalent chromium following oral and intrajejunal doses in rats

The intestinal absorption of trivalent and hexavalent chromium (Cr) given orally (experiment I) or infused in the intestine (experiment II) was investigated in rats. The nonabsorbable form of chromium (51Cr2O3) and water-soluble and more absorbable Na2(51)CrO4 (the hexavalent form of Cr) were compared. Total retention of chromium given orally ranged around 15 percent of the dose, regardless of the chromium compounds applied. The absorption rate of chromic oxide, which is considered a nonabsorbable compound, was 14.4 as a percentage of chromium intake. This result indicates that some loss of chromium has to be taken into account in metabolic trials made by the indicator method. In isolated rat intestine, from the injected Cr 2.5% of chromic oxide and 43.2% of sodium chromate were absorbed during an hour (experiment II). The absorbed chromium was transferred to the liver where the liver tissue retained 10.9% of chromic oxide and 51.1% of sodium chromate. Radioactivity of v. cava caudalis following intestinal injection of Na2CrO4 was thirtyfold greater than after Cr2O3 dosing. This phenomenon can be explained by the lower blood clearance of chromate. Different absorption rate of chromate depending on the route of administration could be due to the fact that the hexavalent form given orally was reduced to Cr3+ in the acidic environment of the stomach. When Na2CrO4 was infused directly in the intestine of rats, such reduction could not occur. This means that the acidic gastric juice might play a role in inhibiting the intestinal absorption of Na2CrO4 when this compound is given orally.     

Non-bioequivalence of various trademarks of enrofloxacin and Baytril in cows

Including Baytril, in various parts of the world many commercial preparations of enrofloxacin for parenteral administration are being employed for the treatment of bacterial diseases in cows. To optimize clinical responses and to minimize development of bacterial resistance to this agent, the copied pharmaceutical preparations must comply with some key pharmacokinetic features when bioequivalence studies are performed. To assess whether or not there was bioequivalence among nine commercial preparations of enrofloxacin and the original one, a controlled pharmacokinetic study was carried out. These was done utilizing the microbiological agar-diffusion test as quantitative/qualitative analytical method. A non-compartmental model defined kinetic variables. Results for Baytril revealed that maximal serum concentration (Csmax) was only matched by one preparation while area under the curve (AUC) of the serum concentration/activity of enrofloxacin and metabolites in time was not matched by any preparation. Time to Csmax (Tmax), elimination half-life, and shape of the time-serum concentrations of enrofloxacin profiles obtained for the nine generic preparations differ significantly somehow from the corresponding data obtained for the reference enrofloxacin. The need for studies to demonstrate bioequivalence becomes mandatory if similar preparations of enrofloxacin become commercially available. Enrofloxacin should be used selectively and cautiously to limit development of bacterial resistance. Non-bioequivalence of relevant pharmacokinetic values, such as Csmax and bioavailability (AUC) would facilitate development of bacterial resistance and limit the useful life span of this antibacterial agent.     

Alteration of body composition in rats: effect of organic chromium and L-carnitine

A growth trial was carried out to test the effect of organic, trivalent chromium and L-carnitine on the body composition of growing rats. At the same time, an evaluation of different measurement methods (weight of epididymal fat pad, adipocyte morphometry, total body electrical conductivity) was performed. Outbred Wistar rats of 30 days of age were fed diets of different (0, 10 and 20%) protein level. The diets were supplemented with 4 mg/kg Cr as chromium nicotinate, and 100 mg/kg L-carnitine. The experimental feeding lasted 15 days, after a 5-day-long adjustment period. It was found that Cr addition increased feed intake. Both treatments caused changes in body composition, increasing fat and protein deposition. Organic chromium had no effect at either protein level, while L-carnitine improved the protein retention only at an optimum (20%) protein supply. No statistically significant correlation was found between total body electrical conductivity (TOBEC) and body composition, which could be attributed to the great individual differences. A close correlation was found among total body fat percentage, weight of epididymal fat pad and the adipocyte surface. The data suggest that there is an interaction between dietary protein supply and the effect of repartitioning agents.     

Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease

Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n=25), inflammatory or infectious (n=13), traumatic (n=8), vascular (n=6), degenerative (n=5), anomalous (n=3) and those with an unremarkable MRI (n=32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7-807).     

The pharmacokinetics and metabolism of ivermectin in domestic animal species

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.     

In Vivo and In Vitro Sperm Interaction with Oviductal Epithelial Cells of Llama

Sperm reservoirs in South American Camelids would be crucial for successful fertilization. Since ovulation occurs approximately 36 h after mating, the maintenance of the sperm viability in the oviduct waiting for the ovum is a critical reproductive event. Our study aimed at determining whether the isthmus or the utero tubal junction (UTJ) could function as a sperm reservoir in llama by means of in vivo and in vitro experiments. For the in vivo experiments, the oviducts of adult females with a dominant follicle bigger than 7 mm were examined for the presence of sperm at 6, 18, 24, 28 and 35 h after mating. The results using scanning and transmission electron microscopy showed ultrastructural differences between isthmus and UTJ with respect to (1) predominance of secretory cells in the UTJ and ciliated cells in the isthmus epithelium and (2) cytoplasmic bulbous projection of the secretory cells in the UTJ. Sperm adhered by a mucus‐like substance were seen only in the UTJ at 6, 18, 24 and 28 h post‐mating. Lack of sperm adhered to oviductal mucosa was observed around ovulation (35 h). In vitro experiments demonstrated higher ability of UTJ epithelial cell explants with respect to isthmus explants to bind sperm in a co‐cultured system. The anatomical features and the presence of a sperm bonding agent in the UTJ together with the in vitro differential binding of sperm to UTJ explants strongly suggest that both may be feasible mechanisms that facilitate sperm storage in this oviductal region in llama.