Cattle elimination

Oral treatment of sheep and cattle (Bos spp.) with diflubenzuron is followed by absorption of the compound through the gastrointestinal tract, metabolism, and elimination of residues through the urine, feces, and, to a very limited extent, milk. Intact diflubenzuron is eliminated in the feces of orally dosed cattle and sheep (Ivie 1978). Major metabolites of diflubenzuron excreted by cattle and sheep result from hydroxylation on the difluorobenzoyl and chlorophenyl rings, and by cleavage between the carbonyl and amide groups to produce metabolites that are excreted free or as conjugates (Ivie 1978). Cattle dosed repeatedly with diflubenzuron had detectable residues only in liver... 

Outcome 2. Suppose, however, that risk attitude is the true driver behind a consumer s reaction to a food safety scare. In such a case, even if probabilities of being exposed to the risk are small, an effective communication of these probabilities will have little influence on a consumer s behavior. Instead, marketers will have to focus on ways to eliminate the risk. This may involve a total recall or an elimination of the risk (slaughtering of all potentially infected cattle or recall of all potentially tainted food). 

High Safety Factor - Authorities have approved Lindane for lice and mange control on dairy cattle. Shows no contamination in milk when properly applied.. . . Even used by dermatologists for human itch, lice and scabies. Not cumulative and practically odorless. Any taken in by a warm-blooded animal is eliminated. 

Although it is not a major elimination route following intravenous or intramuscular injection of penicillin G to dairy cattle, milk constitutes a very important route of elimination following intramammary injection since most of the dose enters milk (58, 59). The persistence of residues in milk does depend on the formulation and route of administration, but, in a wide variety of trials, residues were not found to persist beyond 5 days after the end of treatment (59, 60). Transfer of penicillin G from treated to untreated quarters has also been observed... 

After intramuscular injections of radiolabeled ceftiofur to cattle and swine, the compound was absorbed rapidly into the blood and eliminated mostly in urine (84). The tissue in which highest residue concentrations were observed at 12 h after the last dose was the kidney. Most of the radioactivity was found in the form of the microbiologically active primary metabolite, desfiiroylceftiofur, conjugated to macromolecules in plasma and tissues. Desfiiroylceftiofur cysteine was also found in tissues, plasma, and urine, whereas the desfiiroylceftiofur dimer was found in urine. It was suggested that since the binding of desfiiroylceftiofur to biological molecules is reversible, all of the ceftiofiir-related residues that contain the desfuroylceftiofur moiety have the potential to be microbiologically active. 

The extent to which a sulfonamide is acetylated depends upon the drug administered and the animal species. Acetylsulfathiazole is the principal metabolite found in the urine of cattle, sheep, and swine after enteral or parenteral administration of sulfathiazole. However, sheep can acetylate only 10% of the dose, while cattle can acetylate 32%, and swine 39%. When sulfamethazine was administered intravenously or orally to cattle, the animals eliminated 11% or 25% of the dose, respectively, in urine as N" -acetylsulfamethazine. The increased acetylation that occurred following tlie oral administration may be related to the increased exposure of sulfamethazine to liver enzymes following its absorption into the portal circulation. The acetylation rate may also be affected by the health status of an animal. Tims, cows suffering from ketosis in cows acetylate sulfonamides at much lower extent. 

Sulfadiazine is a relatively short-acting sulfonamide with an elimination half-life of about 3 h in cattle. The importance of this drug for control of furunculoses in fish is determined by its combined use with the potentiator trimethoprim. 

Baquiloprim has a high oral bioavailability in animals where it is widely distributed in the body and slowly eliminated (222,223). In cattle, baquiloprim was reported to have a much longer half-life and a larger volume of distribution than trimethoprim (223). Both urine and bile are important routes of elimination. 

Baquiloprim residue depletion studies in cattle treated by oral and parenteral route and in swine treated by parenteral route showed that 14-42 days after administration, the parent compound amounted to a very small proportion of the total residues in liver, kidney, and at the injection site. This was also the case with all identified metabolites. The concentrations of the residues in fat and normal muscle were too low to permit examination of their presence. However, pig skin contained a relatively high proportion of the parent compound. Pigs generally showed a faster degradation and elimination profile than cattle at comparable times after administration, resulting in lower total and parent drug residue levels. 

Upon intramammary administration to cattle, novobiocin is rapidly absorbed and excreted through milk, feces, and urine. Detectable residues are present in milk for a few days after intramammary infusion, the elimination being highly depended on dosage and formulation. One day after treatment, the concentrations of microbiologically active residues in the liver, kidney, and udder tissue were in the range 1-4 ppm, whereas concentrations in muscle and fat were below 0.1 ppm. 

When tiamulin was given to farm animals by injection, mean elimination half-lives were 3, 3.3, 4.6, and 3.6 h in cattle, buffalo, sheep, and goats, respectively (260, 261). Tiamulin could not be detected at 24 h posttreatment. 

Absorption of fenbendazole is slow in ruminants but more rapid in monogastric animals. Maximum concentrations in blood are achieved at about 8 h in rats and rabbits, 24 h in dogs, and 2-3 days in sheep. Elimination of fenbendazole is predominantly by the fecal route. The metabolic pathway of fenbendazole is similar in rats, rabbits, dogs, sheep, cattle, goats, and chickens. It is rapidly metabolized to fenbendazole sulfoxide (oxfendazole), fenbendazole sulfone, fenbendazole 2-aminosulfone, and other minor metabolites detected in plasma. 

Administered orally, oxibendazole is rapidly absorbed from the gastrointestinal tract. In sheep, the maximum plasma content is reached within 6 h. Much of the dose administered to cattle is eliminated in urine. 

Pharmacokinetic studies (59) in cattle treated with the recommended dosage showed that the drug was well dispersed from the injection site, with less than 1% of the dose remaining at 21 day withdrawal. By 14 days, 87% of the dose was excreted via the bile and feces whereas less than 1% was eliminated via urine. Mean plasma half-life was found to be 6.2 days for the parent compound and 5.9 days for total drug-related residues. 

Following oral administration to cattle, it is absorbed from the gastrointestinal tract, rapidly distributed, metabolized, excreted in the bile, and eliminated in the feces. Residues in liver averaged 0.4 ppm at 12 h after the last dose, whereas residues detected in other tissues were negligible (21). When radiolabeled monensin was administered to steers, essentially all radioactivity was eventually excreted in the feces after conversion to many metabolites that accumulated in the liver (22). 

Pharmacokinetic studies (10) showed that virginiamycin is not significantly absorbed and is eliminated mostly in the feces. Following administration of radio-labeled virginiamycin to rats, turkeys, and cattle, metabolites of the drug appeared in liver of all animals. Most of these metabolites were covalently bound to tissues, whereas the extractable metabolites could not be identified. No residues of virginiamycin could be detected in edible tissues and consequently no withdrawal period has been set up. 

Metabolism leads to their rapid deactivation in tire body and, hence, these compounds exhibit little oral activity. Thus, they have to be given parenterally. Most of the catabolism of these compounds occurs in liver, and enterohepatic circulation may then occur, with the metabolites exerting little if any biological activity. In cattle, most of these compounds are eliminated in feces where 60-90% of the metabolites are found in the free form. In conttast, metabolites occurring in urine are predominantly in conjugated forms. 

Following administration to rat, dog, rabbit, and cow, clenbuterol was rapidly eliminated, being largely excreted in urine in the form of the parent drug (15). Following a 4 day treatment of cattle at the therapeutic dosage (0.8 g/kg bw) and a 7 day withdrawal, concentrations of clenbuterol in liver were at the level of 0.35 ppb or below, whereas concentrations in urine were approximately one-tenth of the levels in liver (16). Administration, on the other hand, of a single oral dose of radiolabeled clenbuterol to cattle showed that 40% of the urinary radioactivity was due to the parent compound. The urinary half-life of clenbuterol in cattle, estimated from the urinary excretion of the parent compound, was approximately 36 h (17). 

Residue depletion studies indicated that different formulations led to different dexamethasone depletion rates. Studies in cattle and pigs indicated that dexa-methasone residues were quickly eliminated from muscle and milk of cows. Residues did not occur in the free form in fat, whereas the depletion rate in liver was the slowest. Following intramuscular administration of 60 g/kg bw to cows, mean dexamethasone levels in milk declined from 8.4 ppb at the first milking after treatment to below 1 ppb at the sixth milking after treatment (52). 

Following oral administration of radiolabeled furosemide, excretion was reported to be almost complete within 3 days in rats (96-98%) and dogs (98-99%). Rat urine contained 40-50% of the parent drug, 30% 4-chloro-5-sulfamoyl-anthranilic acid, and four unidentified metabolites that accounted for the rest of the administered radioactivity. In contrast, urine of dog and monkey contained 85% unmetabolized furosemide, 7% 4-chloro-5-sulfamoyl-anthranilic acid, and the remainder was due to unidentified metabolites. Following intramuscular injection of 5 mg furosemide/kg bw in cattle, the half-life for plasma elimination was estimated at 4.3 h. In contrast, the half-life of furosemide in cattle was reported to be less than 1 h following intravenous administration. 

Residues of methylene blue in edible animal tissues are of public health concern because tliis dye and its metabolites are mutagenic (74). Metabolism studies in cattle have indicated that methylene blue can be eliminated in urine partly unchanged, partly metabolized to leucomethylene blue, or demethylated to N-methyl homologues of thionin, the completely demethylated metabolite of methylene blue, or reduced in vivo and subsequently eliminated in its leuco-form or in one or more chromogenic substances (75). 

The plasma half-life of acetylsalicylic acid varies from 0.8 h in the ruminant to 37.5 h in the cat. This is due partly to the very short elimination in cattle, which is 10 times more rapid in cattle than in most other animals. The clearance is also very high in cattle. 

Pharmacokinetic studies of intravenously administered indomethacin in cattle showed a wide extravascular distribution as suggested by the high volume of distribution and the long elimination half-life observed (99). Similar kinetic behavior of indomethacin was noticed after intramuscular administration in sheep (100). These results suggested that indomethacin could induce high residue levels in tissues. 

In Malaysia there are over 10,000 poultry breeders and 2500 pig farms. Since use of antibiotics is unavoidable for preventing animal diseases, livestock breeders have been told to conform to Good Farming Practices to minimize or eliminate drug residues. As a result, in 1996 only 1.1% of 300 samples taken from 7 poultry processing plants tested positive to antibacterials. Similarly, only 5.7% of 300 samples taken from cattle abattoirs and 17.5% of 300 samples taken from pig abattoirs were tested positive for antibacterial residues. 

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