Pharmacokinetics of eprinomectin in plasma and milk following topical administration to lactating dairy cattle

The pharmacokinetics and mammary excretion of eprinomectin were determined in cattle following topical administration at a dose rate of 0.5 mg kg(-1). The kinetics of plasma and milk concentrations were analysed using a one-compartment model. The maximum plasma concentration of 43.76 ng ml(-1)occurred 2.02 days post administration, and the mean residence time was 4.16 days. Eprinomection was detected in the milk at the first sampling time and thereafter for at least 15 days. Comparison of the milk and plasma data demonstrated the parallel disposition of the drug in the milk and plasma with a milk / plasma concentration ratio of 0. 102+/-0.048. The amount of drug recovered in the milk during this period was 0.109% +/- 0.038 of the total administered dose. This very low extent of mammary excretion resulted in low concentrations of eprinomectin in milk. This supports the permitted use in lactating cattle, as the maximum level of residue in milk did not exceed the maximum acceptable limit of 30 ng ml(-1).     

Role of milk immunoglobulins in the Brucella milk ring test

Milk immunoglobulins were extracted from the stained cream layer of positive milk ring tests from experimentally inoculated or naturally infected cows. IgA was always found, associated with IgM in most cases (15/17) and with IgG in a smaller number of cases (11/17). An additional incubation at 20 degrees C for 18 h gave clearer positive and negative results and a lower limit of detection than that of the usual milk ring test.     

Detection of capsular polysaccharide in milk of cows with natural intramammary infection caused by Staphylococcus aureus

Detection of capsular polysaccharide (CP) in milk of cows with natural intramammary infection caused by Staphylococcus aureus was attempted. Five quarters of 5 cows harboring S aureus strains that produce type-8 CP were selected. Using an ELISA with a monoclonal antibody, type-8 CP was not detected in extracts prepared from fresh milk collected aseptically. By contrast, CP was easily detectable after incubation of infected milk at 38 C for 20 hours. Quantitation of CP in extracts from incubated milk samples by use of ELISA indicated a great variation of CP expression by strains. Although an incubation step was necessary to detect CP, results of the study indicate that CP may be expressed in vivo during intramammary infection caused by S aureus.     

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.     

Description of a new disease on Erythrina sp. in Martinique (French West Indies) and preliminary characterization of the causal agent as a novel Erwinia species

In spring 1995, symptoms of partial defoliation were observed on Erythrina indica var. fastigiata trees, commonly used as windbreaks in banana plantations in Martinique (French West Indies). Browning of the bark surface was consistently observed at the base of defoliated branches. Bacteria were isolated as nearly pure cultures from typical necrotic lesions on the bark. Results of Gram stain, staining of flagella and biochemical tests indicated that all isolates belonged to the Enterobacteriaceae, and to the genus Erwinia . Numerical analysis of the results of 48 biochemical properties showed that Erwinia isolates from diseased erythrina trees constituted a homogenous phenotypic cluster, and that, although weakly pectolytic, these isolates were closely related to pectolytic Erwinia species: E. carotovora ssp. betavasculorum and ssp. wasabiae , and E. cacticida . However, they could be clearly distinguished by different biochemical characteristics from type strains of known plant pathogenic species of Erwinia , Pantoea and Enterobacter . Under greenhouse conditions, the isolates were pathogenic to Erythrina indica var. fastigiata cuttings, but not to banana and pineapple, which are major crops in Martinique.     

Moxidectin in cattle: correlation between plasma and target tissues disposition

The time of parasite exposure to active drug concentrations determines the persistence of the antiparasitic activity of endectocide compounds. This study evaluates the disposition kinetics of moxidectin (MXD) in plasma and in different target tissues following its subcutaneous (s.c.) administration to cattle. Eighteen male, 10-month old Holstein calves weighing 120-140 kg were subcutaneously injected in the shoulder area with a commercially available formulation of MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) at 200 micrograms/kg. Two treated calves were killed at each of the following times post-treatment: 1, 4, 8, 18, 28, 38, 48, 58 and 68 days. Abomasal and small intestine mucosal tissue and fluids, bile, faeces, lung, skin and plasma samples were collected, extracted, derivatized and analysed to determine MXD concentrations by high performance liquid chromatography (HPLC) with fluorescence detection. MXD was extensively distributed to all tissues and fluids analysed, being detected (concentrations > 0.1 ng/g; ng/mL) between 1 and 58 days post-treatment. MXD peak concentrations were attained during the first sampling day. MXD maximum concentration (Cmax) values ranged from 52.9 (intestinal mucosa) up to 149 ng/g (faeces). The mean residence time (MRT) in the different tissues and fluids ranged from 6.8 (abomasal mucosa) up to 11.3 (bile) days. MXD concentrations in abomasal and intestinal mucosal tissue were higher than those detected in plasma; however, there was a high correlation between MXD concentrations observed in plasma and those detected in both gastrointestinal mucosal tissues. MXD concentrations were markedly greater in the mucosa than in its respective digestive fluid (P < 0.01). MXD concentrations in skin were higher than those found in plasma (P < 0.01). Drug concentrations recovered in the dermis were greater than those detected in the hypodermal tissue (P < 0.05). Large concentrations of MXD were excreted in bile and faeces. These findings may contribute to an understanding of the relationship between the kinetic behaviour and the persistence of the antiparasite activity of MXD against different ecto-endoparasites in cattle.     

Lack of Sex-influence on the In Vitro Metabolism of Ivermectin by Hepatic Microsomal Preparations from Cattle

Veterinary Research Communications -     

A commercial extract of fruits and vegetables, Oxxynea, acts as a powerful antiatherosclerotic supplement in an animal model by reducing cholesterolemia, oxidative stress, and NADPH oxidase expression

The effects of fruit and vegetable extract (Oxxynea) on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anion, and NAD(P)H oxidase expression were studied in an animal model of atherosclerosis. Thirty six hamsters were divided into two groups of 18 and fed an atherogenic diet for 12 weeks. They received by gavage either water or Oxxynea in water at a human dose equivalent of 10 fruits and vegetables per day. Oxxynea lowered plasma cholesterol and non-HDL cholesterol, but not HDL-cholesterol, and increased plasma antioxidant capacity. It also strongly reduced the area of aortic fatty streak deposition by 77%, cardiac production of superoxide anion by 45%, and p22phox subunit of NAD(P)H oxidase expression by 59%. These findings support the view that chronic consumption of antioxidants supplied by fruits and vegetables has potential beneficial effects with respect to the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and improving the serum lipid profile.     

The interaction between moxidectin and MDR transporters in primary cultures of rat hepatocytes

The interaction of moxidectin (a macrocyclic lactone, ML) with P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs) and breast cancer resistance protein (BCRP) was studied in primary cultures of rat hepatocytes by measuring the intracellular accumulation of [14C]-moxidectin over 72 h in the presence of specific inhibitors: for P-gp, verapamil (10 microM); for MRPs, MK571 (100 microM), indomethacin (10 microM) and probenecid (3.8 mM); and for BCRP, fumitremorgin C (5 microM). The P-gp and MRP inhibitors increased significantly (P < 0.01) by 48.7%, 49.8%, 49.9% and 57.2% the area under the time-intracellular concentration curve (AUC) of moxidectin in rat hepatocytes, while the BCRP inhibitor, fumitremorgin C, had no effect on the AUC compared with the control. In addition, the mRNAs of all the drug transporters studied were detected in rat hepatocytes from 0 to 72 h. Using this cellular model it has been shown that MRP inhibitors increase moxidectin intracellular concentrations to a similar extent as the P-gp inhibitor. The identification of all the transporters that interact with MLs remains a challenge, which currently concerns several important therapeutic fields.     

Persistence of ivermectin in plasma and faeces following administration of a sustained-release bolus to cattle

Six calves (weight 210 to 230 kg) were dosed with an intra-ruminal slow-release bolus prepared to deliver ivermectin at a low daily dosage for 135 days. Ivermectin concentrations in jugular blood 160 days post-treatment were determined by high performance liquid chromatography (HPLC) using fluorescence detection. Ivermectin plasma concentrations increased gradually to achieve the steady-state concentration (20 ng ml(-1)) at approximately four days post-treatment, which was maintained for 120 days. The ivermectin peak plasma concentration (28.5 ng ml(-1)) was attained at 15 days post-administration of the bolus. The faecal ivermectin concentration rose to a maximal concentration of 4.1 microg g(-1) at four days post-treatment, dropping to a steady-state concentration of around 1.18 microg g(-1) which was maintained up to 120 days post-treatment. Ivermectin was detected in both plasma (0.05 ng ml(-1)) and faeces (2.67 ng g(-1)) up to 160 days. The high levels of ivermectin recovered in faeces indicate that a large proportion of the dose released by the bolus (80 to 90 per cent) is excreted in faeces.