Albendazole in cattle

Albendazole in Cattle Administered via a Sustained-Release Captec Device... 

When sheep were similarly U eated with an oral dose of netobimin, total residues in all tissues except milk were generally lower than those in cattle. Albendazole, albendazole sulfoxide, albendazole sulfone, and albendazole-2-aminosulfone accounted for nearly all the residues in muscle and fat tissues at time points ranging from 18 h to 20 days. In liver and kidney, however, these metabolites accounted for a lower proportion of the total residues as time progressed, indicating the presence of bound residues. 

Oxfendazole, on the other hand, is teratogenic in sheep but not in cattle. Albendazole administered on day 12 in sheep causes exencephaly and on day 17 causes skeletal abnormalities. In sheep, head and face abnormalities tend to occur following exposure from day 12 to 17, spinal column defects from day 16 to 21, and limb distortion from day 22 to 25. 

Depending on the species, parbendazole, mebendazole, albendazole, oxfendazole, cambendazole, and febantel can be teratogenic in the parent form or indirectly from metabolite formation. Oxibendazole and fenbendazole in parent form are not teratogenic, although one of the metabolites of fenbendazole, a sulfoxide found in the milk of cows treated with fenbendazole, is teratogenic in the rat and sheep. Albendazole displays similar biotransformation pathways in cattle as it does in sheep, yet the bovine animal is refractory to its teratogenic effect at normal dosage rates. 

Albendazole (ABZ) is one of a class of benzimidazoles used to control helminth infections in cattle. It is generally administered as a single oral dose of 10 mg/kg b.w. either by bolus or drench. The residue levels and plasma pharmacokinetic profiles resulting from a single dose of ABZ are well documented (7). Recent studies have made important progress into alternative methods of anthelmintic... 

The level of marker residue(ABZ-NH2) was determined using the approved regulatory method entitled "Quantification of Albendazole Marker Residue in Cattle Liver Tissue Using a Fluorescence HPLC Method" (6). 

For several other protozoan diseases there is adequate chemotherapy the 5-nitroimidazoles (for example, metronidazole) for the treatment of amoebiasis, giardiasis and trichomoniasis, the hydroxy-naphthoquinone bupravaquone for theileriosis in cattle and other ungulates, and the polyene ionophores (for example monensin, lasalocid, narasin and salinomycin) for the prophylaxis of avian coccidiosis. However, improved therapies are required for some opportunistic parasites that cause disease in immunocompromised humans. Paromomycin and nitazoxanide have some effect in the treatment of cryptosporidiosis and albendazole appears to be effective for microsporidiosis caused by Encephalitizoon intestinalis. 

Albendazole is widely used in sheep and cattle for treating roundworms and flukes at oral dosages that range from 5 to 10 mg/kg bw. Albendazole and its sulfoxide metabolite exhibit teratogenic effects in animals. 

Residue depletion studies in dairy cattle and sheep showed that the proportions of the major sulfoxide, sulfone, and 2-aminosulfone metabolites of albendazole change dramatically over a period of days in the case of tissues or hours in the case of milk, with albendazole sulfoxide predominating at early time points and albendazole sulfone and albendazole-2-aminosulfone appearing later (16). From day 4 onwards, more than 95% of the residues in bovine liver and kidney was in the bound form, but tissue binding in sheep tissues was less extensive. 

Netobimin is an albendazole prodrug intended for use in sheep and cattle. An oral dosage of 7.5 mg/kg bw is recommended for treatment of gastrointestinal infestations by roundworms and tapeworms, and 20 mg/kg bw for type II ostertag-iosis and adult flukes. Netobimin exhibits teratogenic effects in animals. 

After subcutaneous or intramuscular injection of netobimin into cattle, absorption was rapid but plasma levels of radioactivity were lower than those achieved following oral administration. This indicates that absorption occurred prior to the conversion to albendazole since high levels of parent drug were found in plasma and milk soon after the injection. On the other hand, at 12 h after the injection the parent drug could not be detected at the injection site or in liver. 

This group of compounds has played an important role in the control of worm infestations of cattle, sheep and horses, with particular activity against the larval stages of worms. Prior to their introduction there was no effective treatment of larval stages of worms. The benzimidazoles are also active against tapeworms and fluke. The main compounds in use are thiabendazole, cambendazole, fenbendazole, oxfendazole, mebendazole and albendazole. The mode of action of these compounds is through their effect on the uptake of nutrients by the helminth, which results in a reduction in glycogen and subsequent starvation. 

Albendazole and fenbendazole, prochiral sulphide benzimidazole anthelmintics, are metabolically converted (sulphoxidation) to the corresponding active sulphoxide metabolites, each of which exists in the plasma as two enantiomers. Sulphoxide benzimidazoles have a chiral centre around the sulphur atom in their molecules. The sulphoxide metabolites (enantiomers) are irreversibly metabolized (sulphonation) to inactive sulphones. This pathway of hepatic biotransformation has been shown to occur both in ruminant (sheep, goats, cattle) and monogastric (man, dogs, rats) species (Delatour et al., 1991b,... 

Delatour, P., Gamier, F., Benoit, E. Caude, I. (1991b) Chiral behaviour of the metabolite albendazole sulphoxide in sheep, goats and cattle. Research in Veterinary Science, 50, 134-138. 

Albendazole (20) The drug possesses broad-spectrum of activity against different nematodes, cestodes and trematodes in sheep and cattle. It removes intestinal tapeworms from sheep at doses ranging from 3.8-7.5 mg/kg. However, a dose of 50 mg/kg is required to eliminate larval T. saginata from cattle [176]. 

The activity of benzimidazoles against trematodes is less pronounced as compared to nematodes and cestodes. However, albendazole (20) and the newly introduced triclabendazole (23) find use in treating liver fluke infections in sheep and cattle [4,5,57,175]. 

Albendazole (20) The drug shows high activity against Fasciola spp. in sheep and cattle at an oral dose of 4.75 and 10 mg/kg, respectively. However, its activity is restricted to fully grown adult flukes only. This makes albendazole unsuitable for treating acute fascioliasis in animals. The drug also exhibits more than 98% activity... 

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