Comparative plasma and milk dispositions,faecal excretion and efficacy of per os ivermectin and pour‐on eprinomectin in horses

The horse milk gains increasing interest as a food product for sensitive consumers, such as children with food allergies or elderly people. We investigated the plasma and milk disposition, faecal excretion and efficacy of per os ivermectin (IVM) and pour‐on eprinomectin (EPM) in horses. Ten mares were divided into two groups. The equine paste formulation of IVM and bovine pour‐on formulation of EPM were administered orally and topically at dosage of 0.2 and 0.5 mg/kg bodyweight. Blood, milk and faecal samples were analysed using high‐performance liquid chromatography. The plasma concentration and persistence of IVM were significantly greater and longer compared with those of EPM. Surprisingly, EPM displayed a much higher disposition rate into milk (AUC_milk/plasma: 0.48) than IVM (AUC_milk/plasma: 0.19). IVM exhibited significantly higher faecal excretion (AUC_faeces: 7148.54 ng·d/g) but shorter faecal persistence (MRT_faeces: 1.17 days) compared with EPM (AUC_faeces: 42.43 ng·d/g and MRT_faeces: 3.29 days). Faecal strongyle egg counts (EPG) were performed before and at weekly intervals after treatment. IVM reduced the EPG by 96–100% for up to 8 weeks, whereas the reduction in the EPM group varied from 78 to 99%. In conclusion, due to the relatively low excretion in milk, EPM and IVM may be used safely in lactating mares if their milk is used for human consumption. Nevertheless, much lower plasma and faecal availabilities of EPM could result in subtherapeutic concentrations, which may increase the risk of drug resistance in nematodes after pour‐on EPM administration compared with per os IVM.     

A field study on the efficacy of doramectin against strongyles and its egg reappearance period in horses

The aim of the present study was to determine the efficacy and the so-called "egg reappearance period" (ERP) of doramectin in horses naturally infected with strongyles during a period of 34 weeks. A group of yearlings of 10 animals was treated intramuscularly with doramectin at a dose rate of 0.2 mg/kg bodyweight (BW) at the begin of the grazing season. To obtain comparable data, another group of yearlings (n = 10) was treated orally with ivermectin at a dose rate of 0.2 mg/kg BW. Individual faecal samples were examined for strongyle egg counts per gram of faeces (EPG) in two-week intervals. Twelve weeks later, a second treatment was given in both groups with the respective anthelmintic followed by a third treatment when the group mean egg count reached > or = 200 EPG. The efficacy of doramectin was > or = 96 % and that of ivermectin 100%, based on the mean egg counts two weeks post treatments (wpt). The highest and the lowest extensity of the efficacy (average values) for doramectin were 90% and 41% two and ten wpt, respectively, whereas these values for ivermectin differed from 100% (two wpt) to 24.3% (eight wpt). The ERP was found to be 10 and 8 weeks for doramectin and ivermectin, respectively.     

Organic Glasses: A New Class of Photorefractive Materials

The performance of amorphous organic photorefractive (PR) materials in applications such as optical data storage is generally limited by the concentration of active molecules (chromophores) that can be incorporated into the host without forming a crystalline material with poor optical quality. In polymeric PR systems described previously, performance has been limited by the necessity of devoting a large fraction of the material to inert polymer and plasticizing components in order to ensure compositional stability. A new class of organic PR materials composed of multifunctional glass-forming organic chromophores is described that have long-term stability and greatly improved PR properties.     

Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens

AIMS: To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration.

METHODS: Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2?mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC.

RESULTS: Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (p<0.01). The time to maximum concentration and elimination half-life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days, respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively) administration (p<0.01). IVM was first detected in eggs 2 days after treatment in all groups and was detected until 8 days after oral and I/V administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9?µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE: The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.     

Comparison of conventional coproscopical methods and commercial coproantigen ELISA kits for the detection of Giardia and Cryptosporidium infections in dogs and cats

Faecal samples of 270 dogs and 100 cats from 3 animal shelters in Germany were comparatively examined using conventional coproscopical methods and commercial coproantigen ELISA kits for the detection of Giardia and Cryptosporidium infections. Giardia cysts were found in 9.5% and 0% of the faecal samples in dogs and cats, respectively, examined once using the ZnCl2-NaCl flotation. However, the Giardia coproantigen ELISA (ProSpecT Giardia Microplate Assay) was positive in 29.5% and 22.4% of the samples from dogs and cats, respectively. Direct faecal smears stained with carbol fuchsin showed Cryptosporidium oocysts in one dog (0.4%) and one cat (1%). In contrast, the Cryptosporidium coproantigen ELISA (ProSpecT Cryptosporidium Microplate Assay) reacted positively in 23% of the samples from dogs and 30% of the samples from cats. Both coproantigen ELISAs were more often positive in coproscopically Giardia-negative canine faecal samples that contained Isospora burrowsi/ohioensis oocysts than in faecal samples without any parasite stage. Possible reasons for these observations are discussed.     

Plasma Disposition and Faecal Excretion of Netobimin Metabolites and Enantiospecific Disposition of Albendazole Sulphoxide Produced in Ewes

Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high-performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and albendazole sulphone (ABZSO₂) metabolites were detected in the plasma samples. Maximum plasma concentrations (C<_max) of ABZSO (4.1 ± 0.7 μg/ml) and ABZSO₂ (1.1 ± 0.4 μg/ml) were detected at (t _max) 14.7 and 23.8 h, respectively following oral administration of netobimin. The area under the curve (AUC) of ABZSO (103.8 ± 22.8 (μg h)/ml) was significantly higher than that ABZSO₂(26.3± 10.1 (μg h)/ml) (p<0.01). (−)−ABZSO and (+)-ABZSO enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO (87.8±20.3 (μg h)/ml) was almost 6 times larger than that of (−)−ABZSO (15.5 ±5.1 (μg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was predominant and its AUC was significantly higher than that of ABZSO and ABZSO₂, following NTB administration in faecal samples (p > 0.01). Unlike in the plasma samples, the proportions of the enantiomers of ABZSO were close to racemic and the ratio of the faecal AUC of (−)−ABZSO (172.22 ±57.6 (μg h)/g) and (+)-ABZSO (187.19 ±63.4 (μg h)/g) was 0.92. It is concluded that NTB is completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is completely metabolized to its sulphoxide and sulphone metabolites by first-pass effects. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver that are responsible for sulphoxidation and sulphonation of ABZ.     

Ecological role of the giant root‐rat (Tachyoryctes macrocephalus) in the Afroalpine ecosystem

Rodents with prevailing subterranean activity usually play an important role in the ecosystems of which they are a part due to the combined effect of herbivory and soil perturbation. This is the case for the giant root‐rat Tachyoryctes macrocephalus endemic to the Afroalpine ecosystem of the Bale Mountains, Ethiopia. We studied the impact of root‐rats on various ecosystem features within a 3.5‐ha study locality dominated by Alchemilla pasture, which represents an optimal habitat for this species, in 2 periods of a year. The root‐rats altered plant species composition, reducing the dominant forb, Alchemilla abyssinica, while enhancing Salvia merjame and a few other species, and reduced vegetation cover, but not the fresh plant biomass. Where burrows were abandoned by root‐rats, other rodents took them over and A. abyssinica increased again. Root‐rat burrowing created small‐scale heterogeneity in soil compactness due to the backfilling of some unused burrow segments. Less compacted soil tended to be rich in nutrients, including carbon, nitrogen and phosphorus, which likely affected the plant growth on sites where the vegetation has been reduced as a result of root‐rat foraging and burrowing.     

Oscillatory thermomechanical instability of an ultrathin catalyst

Because of the small thermal capacity of ultrathin ( approximately 200 nanometers) metal single crystals, it is possible to explore the coupling of catalytic and thermal action at low pressures. We analyzed a chemothermomechanical instability in this regime, in which catalytic reaction kinetics interact with heat transfer and mechanical buckling to create oscillations. These interacting components are separated and explored through experimentation, mathematical modeling, and scientific computation, and an explanation of the phenomenon emerges from their synthesis.     

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats

Gokbulut, C., Cirak, V.Y., Senlik, B., Aksit, D., McKellar, Q.A. The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour‐on administration in goats. J. vet. Pharmacol. Therap. 34 , 70–75. The effects of different ages and dosages on the plasma disposition and hair degradation of ivermectin (IVM) were investigated following pour‐on administration in goats. Twenty‐eight female Saanen goats allocated into two groups of 14 animals according to their ages as young (5–6 months old) and old (12–24 months old) groups. Each age group was divided into two further of seven goats and administered pour‐on formulation of IVM topically at the in recommended dosage rate of 0.5 mg/kg bodyweight The recommended cattle dosages rate of 0.5 mg/kg or at the higher dosage of 1.0 mg/kg. Blood samples were collected at various times between 1 h and 40 days. In addition, hair samples (>0.01 g) were collected using tweezers from the application sites and far from application sites of the all animals throughout the blood sampling period. The plasma and hair samples were analyzed by high performance liquid chromatography (HPLC) using fluorescence detection following solid and liquid phase extractions, respectively. Dose‐ and age‐dependent plasma disposition of IVM were observed in goats after pour‐on administration. In addition, relatively high concentration and slow degradation of IVM in hair samples collected from the application site and far from the application site were observed in the present study. The differences between young and old goats are probably related to differences in body condition and/or lengths of haircoat. The systemic availability of IVM following pour‐on administration is relatively much lower than after oral and subcutaneous administrations but the plasma persistence was prolonged. Although, the longer persistence of IVM on hairs on the application site may prolong of efficacy against ectoparasites, the poor plasma availability could result in subtherapeutic plasma concentrations, which may confer the risk of resistance development in for internal parasites after pour‐on administration in goats.     

Pharmacological assessment of netobimin as a potential anthelmintic for use in horses: Plasma disposition, faecal excretion and efficacy

This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10 mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster’s technique before and after the treatment. Neither NTB nor ABZ were present and only albendazole sulphoxide (ABZSO) and sulphone metabolites (ABZSO₂) were detected in the plasma samples. Maximum plasma concentration of ABZSO (0.53 ± 0.14 μg/ml) and ABZSO₂ (0.36 ± 0.09 μg/ml) were observed at (t_max) 10.50 and 19.50 h, respectively following administration of NTB. The area under the curve (AUC) of the two metabolites was similar to each other. Netobimin was not detected, and ABZ was predominant in faecal samples. The maximum plasma concentration (C_max) of (−)ABZSO was significantly higher than (+)ABZSO, but the area under the curves (AUCs) of the enantiomer were not significantly different each other in plasma samples. The enantiomers of ABZSO were close to racemate in the faecal samples analyzed. Netobimin reduced the EPG by 100%, 100%, 77%, 80% and 75% 2, 4, 6, 8 and 10 weeks post-treatment, respectively. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver which are responsible for sulphoxidation and sulphonation of ABZ. Considering the pharmacokinetic and efficacy parameters NTB could be used as an anthelmintic in horses.