Anticoccidials lasalocid

Polyethers. Antibiotics within this family contain a number of cycHc ether and ketal units and have a carboxyHc acid group. They form complexes with mono- and divalent cations that ate soluble ia aoapolar organic solvents. They iateract with bacterial cell membranes and allow cations to pass through the membranes causiag cell death. Because of this property they have been classified as ionophores. Monensia, lasalocid, and maduramicia are examples of polyethers that are used commercially as anticoccidial agents ia poultry and as growth promotants ia mmiaants. 

Anticoccidial Activity. The 1968 report that claimed monensin has activity against Eimeria sp., particularly E. tenella E. macdma., and E. acervulina greatly altered the prevention and control of coccidiosis in poultry (172). It is estimated that the polyether ionophores presently constitute more than 80% of the total worldwide usage of anticoccidials (173). Lasalocid and monensin have been approved for use in control of coccidiosis in cattle. 

Table 3 Hsts the polyether antibiotics used as poultry anticoccidial dmgs in the United States. Recendy, lasalocid and monensin have been approved for use in bovine coccidiosis at levels in feed of 11—33 g/t.

Other anticoccidials for which immunoassays have been developed include the polyethers salinomycin and lasalocid, and the quinazoline drug halofuginone. Concern over the potential toxicity of salinomycin has led to development of two competitive ELISAs for detecting and measuring salinomycin residues in poultry tissues. In the first ELISA (96), 16 monoclonal antibodies were prepared and evaluated for their ability to produce a rapid and low-cost screening procedure for residues of salinomycin in poultry liver. In the second (97), the antibodies produced showed cross-reactivity with narasin but not with lasalocid, madura-... 

Cleanup and concentration of both polar and nonpolar anticoccidial drugs from coextracted substances have mainly been accomplished with polar sorbents, such as silica (379, 391, 396, 398, 399, 402, 407, 410, 411), alumina (227, 257, 403, 404, 406, 412), or Florisil (388), since they provide high recovery of the analytes. However, in many cases, cation exchange sorbents (409), reversed-phase sorbents (405), or combinations of silica with reversed-phase sorbents (395, 400), alumina with Sephadex LH-20 (406), or alumina with Sephadex LH-20 and silica (397, 401) sorbents have been reported to be a powerful approach for the isolation and/or cleanup of these compounds. It is significant to note that cleanup systems using alumina are not suitable for isolation of lasalocid residues since they are irreversibly bound to the sorbent. 

Gas chromatographic separation has not gained wide acceptance in spite of being quite sensitive and specific. This mode of separation is complicated by the necessity for derivatization of anticoccidials before analysis. The hydroxy metabolite of dimetridazole is subjected to derivatization via esterification with acetic acid/sulftiric acid mixture (402), while lasalocid is derivatized via silylation with N,0-Bis(trimethylsilyl)trifiuoroacetamide (BSTFA) (387). This derivatization step is required not only to form the volatile derivatives of these drugs but also to improve their chromatographic properties (thermal stability and decreased polarity). 

Despite almost 10 years of intensive use in the production of broilers, this drug is remarkably free of resistance problems. Other ionophores have been tested and found to possess anticoccidial activity. Lasalocid (64) is in commerical use whilst salinomycin (65) and narasin (66) have recently been evaluated in field trials. 

Ionophores, or polyether (PET) antibiotics, produced by various species of Streptomyces, possess broad spectrum anticoccidial activities. They are chemically characterized by several cyclic esters, a single terminal carboxylic acid group, and several hydroxyl groups. Representative members of this class include salinomycin (SAL), monensin (MON), lasalocid (LAS), narasin (NAR), maduramicin (MAD), and semduramicin (SEM). The main chemical properties of interest in the extraction methodology are their low polarities and instability under acidic conditions. They are able to form stable complexes with alkaline cations. All of these compounds, with the exception of LAS, bind monovalent cations (e.g., Na+ and K+). Lasalocid has a tendency to form dimers and can form complexes with divalent cations such as Mg2+ and Ca2+. The formation of metal complexes results in all of these compounds adopting a quasi-cyclic formation consequent to head-to-tail hydrogen bonding. No MRLs have yet been set by the EU for any of the carboxylic acid PETs (98). 

Coccidiosis is a protozoal disease of the intestinal tract of animals that leads to severe loss of productivity and death. The development and widespread use of anticoccidials has revolutionized the poultry industry. The estimated world market for anticoccidial agents in 1989 was 425 million and this was dominated by the polyether ionophore antibiotics monensin, salinomycin [53003-10-4], narasin [55134-13-9], lasalocid, and maduramicin [84878-61-5] (26). 

Polyether lonophores. Isolation and identification of antibiotic X-14885A was reported.Its structure is closely related to A-23187 and cezomycin, members of the pyrrolether class of natural ionophores. Aspects of the discovery and ionophoric properties of the X-14868 complex were described. Another new naturally derived agent, CP-53607 (32), was reported to be effective t ainst coccidia and as a rumen propionic acid stimulant. The C-26 urethane analogs of monensin transported both Rb and Ca. Their antibacterial and anticoccidial activities were also reported as greater than monensin. Microbial conversion of grisorixin by Streptomyces rimosus was found to produce an inactive and detoxified product. A unified stereochemical model of polyether antibiotic structure and biogenesis was proposed. Ibtal synthesis of ionophores continued to be of interest and the unnatural enantiomer of lasalocid A was found to have similar biolc cal properties to the natural product. ... 

Other veterinary drugs Other veterinary drugs of importance are the anticoccidial feed additives such as the ionophores, narasin, monensin, salinomycin, apramycin, lasalocid, and nicarbazin. The USDA/ FSIS have a method for the major ionophores in tissue samples, which is based on purification of sample extracts by silica gel, alumina, or ion-ex-change column chromatography and determination by TEC with detection by bioautography. A number of alternative methods based on immunoassays, biosensor technology, and HPLC have been developed. 

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