Effect of age and gender in the pharmacokinetics of albendazole and albendazole sulphoxide enantiomers in goats

The kinetics of albendazole metabolites and albendazole sulphoxide enantiomers were studied in 2- and 14-month-old female and male goats, after a single oral dose administration (10 mg/kg) of an albendazole formulation. Blood samples from the jugular vein were collected at 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 and 54 h post-treatment and analyzed using a high performance liquid chromatography method. In all groups the area under the plasma concentration-time curve (AUC) and peak concentration (C_max) values of (+)-ABZSO were significantly higher than those of (−)-ABZSO. The AUC and C_max values obtained for (+)-ABZSO and (−)-ABZSO in adult animals were higher compared to the results in young animals, showing significant differences except for (+)-ABZSO in female animals. In young animals, independently of gender, the C_max appeared earlier compared to adult animals. The mean residence time (MRT) values were shorter in young animals compared to adult animals for all compounds analyzed. No sex-related differences were found for any of the parameters calculated except for the (+)-ABZSO from adult animals.     

Placental transfer of albendazole sulphoxide enantiomers in sheep

Albendazole sulphoxide (ABZSO) is an anthelmintic drug used in veterinary practice. Its molecule has a chiral centre in the sulphur atom and racemic formulations are always used. The kinetics of the ABZSO enantiomers in the last third of pregnancy in ewes, and the placental transfer to the fetus, were studied after a single-dose oral administration (7.5 mg/kg) of a racemic formulation. In mothers, the area under the plasma concentration-time curve (AUC) and C(max) values of (+)-ABZSO (42.4+/-10.5 microg/mL and 1.9+/-0.4 microg/mL, respectively) were higher than those of (-)-ABZSO (15.3+/-5.1 microg/mL and 1.0+/-0.3 microg/mL). The MRT values were 17.0+/-1.6 h for (+)-ABZSO and 13.1+/-1.8 h for (-)-ABZSO. Similar kinetic parameters were obtained in the fetus for both enantiomers, but the fetal concentrations were lower compared with values for the dam. The AUC ratio between (-)-ABZSO/(+)-ABZSO in the dam was 0.36 and in the fetuses 0.64, indicating a higher impairment for the (+)-enantiomer in its placental transfer to the fetus.     

In vivo and ex vivo uptake of albendazole and its sulphoxide metabolite by cestode parasites: relationship with their kinetic behaviour in sheep

The current experiments correlate the disposition kinetics of albendazole (ABZ) following its intravenous (i.v.) and intraruminal (i.r.) administrations to Moniezia spp.-infected sheep, with the pattern of drug/metabolite uptake by tapeworms collected from treated animals. The ex vivo uptake pattern of ABZ and albendazole sulphoxide (ABZSO) by the same cestode parasite was also investigated. Naturally infected (Moniezia spp.) Corriedale lambs were treated with ABZ by either i.v. (Group A, n = 15) or i.r. (Group B, n = 15) administration at 7.5 mg/kg. Plasma and abomasal fluid samples were obtained over a 120-h period. Two animals per group were killed at 0.5, 1, 2, 4 and 6 h post-treatment; parasite material (tapeworms), bile and intestinal fluid samples were recovered. Furthermore, Moniezia spp. tapeworms obtained from sheep killed at the local abattoir were incubated with either ABZ or ABZSO for different time periods in a Kreb's Ringer Tris buffer (ex vivo experiments). Samples were analysed by high performance liquid chromatography for ABZ, ABZSO and albendazole sulphone (ABZSO2). ABZ plasma concentrations decreased rapidly and were not detectable beyond 10 h following i.v. administration. ABZSO and ABZSO2 were the metabolites recovered in plasma after both treatments. ABZ and its metabolites were extensively distributed to the digestive tract, mainly into the abomasal fluid, after the i.v. and i.r. administrations. The parent drug and its active ABZSO metabolite were recovered in tapeworms collected from both i.v. and i.r. treated lambs. However, the availability of both ABZ and ABZSO was higher in parasite material recovered from i.v. treated animals. The uptake of ABZ by the cestode parasite, both in vivo and ex vivo, was significantly greater than that of its sulphoxide metabolite, which agrees with the higher lipophilicity of the parent drug.     

Chirality of the sulphoxide metabolites of fenbendazole and albendazole in sheep

Two prochiral sulphide drugs, fenbendazole (FBZ) and albendazole (ABZ) were administered orally to sheep. Blood samples were analysed for parent drug and S-oxidation metabolites and the chirality of the sulphoxide metabolites was determined. The plasma concentrations of the enantiomers of the sulphoxides were never a racemate. On the contrary, the ratios were greater than 1 as soon as the sulphoxide compounds could be detected in plasma. They subsequently increased linearly throughout the time course of the kinetics, reaching the level 86:14 after FBZ and 95:5 after ABZ treatment. The major enantiomer represented 74% and 86% of the total AUC of SO.FBZ and SO.ABZ, respectively.     

Uptake of albendazole and albendazole sulphoxide by Haemonchus contortus and Fasciola hepatica in sheep

The pattern of in vivo uptake of albendazole (ABZ) and its major metabolite, ABZ-sulphoxide (ABZSO), by Haemonchus contortus and Fasciola hepatica recovered from ABZ-treated sheep, was investigated. Concentration profiles of both compounds were simultaneously measured in target tissues/fluids from the same infected sheep. In addition, the proportion of the (+) and (-) ABZSO enantiomers was determined in plasma, bile and F. hepatica recovered from treated sheep. Sheep naturally infected with H. contortus were intraruminally (i.r.) treated with ABZ (micronized suspension, 7. 5mg/kg) and the plasma concentrations of ABZSO and ABZ-sulphone (ABZSO(2)) determined in addition to the concentration of ABZ and ABZSO in H. contortus, abomasal mucosa and fluid content samples. In addition, F. hepatica artificially infected sheep were treated i.r. with the same ABZ suspension (7.5mg/kg), and samples of blood, bile, liver tissue and adult flukes were collected and analysed by HPLC to determine the concentrations of ABZ and both enantiomers of ABZSO. ABZSO and ABZSO(2) were the analytes recovered in plasma with ABZ and ABZSO present in H. contortus. ABZ was the analyte recovered at the highest concentration in H. contortus and abomasal mucosa, whereas higher concentrations of ABZSO were measured in abomasal fluid content. Only low concentrations of ABZ were detected in F. hepatica and bile, but markedly higher concentrations of ABZ were measured in liver tissue. ABZSO was the main molecule recovered in F. hepatica, plasma and bile samples collected from ABZ-treated sheep. The (+) enantiomer of ABZSO was recovered at a higher proportion in plasma (75%), bile (78%) and F. hepatica (74%) after ABZ administration to infected sheep.     

Lung sounds in cattle, horses, sheep and goats

The purpose of this paper is to emphasize the importance of pulmonary auscultation for the clinician. It suggests a clarification and simplification of the terminology to be used which would be helpful to veterinary students and allow better communications between veterinarians. The interpretation of these sounds and the relationships to conditions and diseases of the lungs in cattle, horses, sheep and goats are discussed.     

Lysozyme concentrations in the tears of cattle, goats, and sheep

Tear samples were collected from 1 eye of each of 40 cows, 27 sheep, 5 goats, and 5 human beings. Additionally, 10 bovine tear samples were pooled and concentrated. Spectrophotometric assays, using Micrococcus lysodeikticus, were performed on each sample to detect lysozyme activity expressed in hen egg lysozyme (HEL) equivalents. Lysozyme activity was not detected in tears of cows, but 158.8 +/- 159.3 mg of HEL/ml was detected in tears of sheep, 220.7 +/- 37.5 mg of HEL/ml in tears of goats, and 216.3 +/- 86.2 mg of HEL/ml in tears of human beings. In pooled bovine tear samples, lysozyme activity was not detected on plate assay and lysozyme protein was not detected on polyacrylamide gel electrophoresis, column chromatography, or immunoelectrophoresis with rabbit anti-bovine tear antibodies. On the basis of these observations, we concluded that the basic ocular protective mechanism in bovine tears is not lysozyme. Other anti-bacterial proteins such as lactoferrin, transferrin, complement, or beta-lysin may, therefore, be of primary importance in protecting the bovine eye.     

Comparison of pepsinogen forms in cattle, sheep and goats

Different types and subtypes of pepsinogen extracted from bovine, ovine and caprine abomasa were found to differ according to their phosphate content and relative molecular mass (Mr). Bovine pepsinogens had organic phosphate contents ranging from 1.65 to 2.22 mol of phosphate mol-1 of pepsinogen. Ovine pepsinogens were in the range 1.50 to 2.36 and caprine pepsinogens were in the range 1.42 to 2.00. The major types of pepsinogen from each species were different in size. Bovine pepsinogen had an Mr of 39,000, ovine had an Mr of 43,000 and caprine pepsinogen had an Mr of 42,000.     

Dynamics of digestion in cattle, sheep, goats and deer

Four experiments were conducted to study factors affecting digestibility of forages in cattle, sheep, goats and white-tailed deer. In a series of digestion trials (Exp. 1), the dry matter digestibility of a moderately high fiber diet was greater in cattle than in deer. Digestibilities of the diet in sheep and goats were intermediate and not different from either extreme. In a second series of trials (Exp. 2), relative organic matter digestibilities were for goats more than sheep more than deer. However, in Exp. 2, intake in goats was very low and digestibility appeared to be positively related to retention time and inversely related to turnover rate. Results of three trials (Exp. 3) suggested that rate of digestion was related more to diet than to the animal species consuming the diet. In grazing animals (Exp. 4), goats digested a smaller percentage of consumed material than either cows or sheep during three of four seasons even though diets were of similar in vitro digestibility. This difference was related to a faster turnover and shorter retention time in goats. These data support the concept that there are species differences in gastrointestinal dynamics which may be which may be important determinants of adaptability to grazing conditions.     

Toxoplasmosis in sheep,goats and cattle in central Ethiopia

In a seroepidemiological survey using an indirect haemagglutination assay, the prevalence rate of toxoplasmosis in central Ethiopia was 22.9% of 899 sheep, 11.6% of 753 goats and 6.6% of 785 cattle. There were high titres of 1:256 or more which suggest current infections. These results indicate that toxoplasmosis may be an important cause of reproductive wastage in small ruminants. The public health significance of this disease is discussed. Improved hygiene and management could reduce the prevalence of the disease.     

Pharmacokinetic comparison of six anthelmintics in sheep,goats, and cattle

This study was initiated to determine whether a comparative pharmacokinetic (PK) approach could be used to expand the pool of approved anthelmintics for minor ruminant species. Accordingly, the PK profiles of six anthelmintics (levamisole, albendazole, fenbendazole, moxidectin, doramectin, and ivermectin) in sheep, goats, and cattle were determined. The PK values determined for each anthelmintic included T_max, T_last, C_max, AUC, AUC/dose, and C_max/dose. The results of this study demonstrate that a comparative PK approach does not show commonality in the way these six anthelmintics are individually processed by these three ruminants. While some drugs demonstrated identical PK profiles between sheep and goats, none of these drugs demonstrated PK profiles in sheep and goats comparable to the PK profiles found in cattle. The results from this study suggest drug approval across these three ruminants is not a viable concept. However, the resulting PK profiles for each combination of drug and ruminant species represents a new dataset that can be used to support the US FDA Center for Veterinary Medicine's Minor Use/Minor Species indexing process for drug approvals in minor species such as sheep and goats.     

Bioavailability of albendazole sulphoxide after netobimin administration in sheep: effects of fenbendazole coadministration.

After oral co-administration of two dosages of netobimin (7.5 and 20 mg kg-1 with fenbendazole (1.1 mg kg-1) to Merino sheep, the AUC0-infinity of albendazole sulphoxide at the lower dosage of netobimin, was significantly increased (75.5 per cent) from control value (34.43 +/- 7.91 versus 60.33 +/- 11.93 microg h ml-1). The pharmacokinetic parameters MRT and T1/2 were also increased: 18.96 +/- 2.54 vs 26.44 +/- 4.69 h and 10.31 +/- 1.72 vs 22.28 +/- 6.75 h respectively. No data corresponding to the higher dosage of netobimin (20 mg kg-1) were statistically different from control values. It is concluded that fenbendazole increases the bioavailability of albendazole sulphoxide in sheep at the 7.5 mg kg-1 dosage, and this may produce a potentiated anthelmintic action.     

Field evaluation of a mixture of albendazole sulphoxide and levamisole against Ostertagia and Trichostrongylus spp in sheep

The efficacy of a mixture of albendazole sulphoxide and levamisole, 3.6 and 8.25 mg/kg respectively, at single and double dose rates, was compared with the recommended dose rate of each anthelmintic alone. The comparison was conducted on groups of 6 to 14-week-old lambs on 22 farms, 16 of which had evidence of multiple resistance to benzimidazole and levamisole. A single dose of the mixture reduced mean egg counts by 95% on half the farms with multiple resistance and on all the remaining farms. Consequently, the mixture should be included in an assessment of effective anthelmintics on farms to determine its value for nematode control. A double dose rate of mixture was effective on all but 4 farms. Reductions caused by the mixture were due to the additive actions of the drugs on 18 of 22 farms; synergistic action was noted on only 3 farms. It was concluded that the mixture of albendazole sulphoxide and levamisole offered many farmers an effective anthelmintic for use in preventive control programs. Recommendations for such programs include annual rotation of effective anthelmintics as a means of delaying selection for drug resistance.