Animals dosed with acetaminophen

Localization of Drug-Protein Adducts in Animals Dosed with the Prototype Hepatotoxin, Acetaminophen... 

In humans, exposure to paracetamol (acetaminophen) is primarily by the oral route from a wide variety of formulations (tablets, capsules and liquids) either on its own or in combination with other drugs. An estimate of paracetamol (acetaminophen) consumption [prescribed paracetamol (acetaminophen), combination tablets and paracetamol (acetaminophen) without a prescription] was 3500 million 500 mg tablets in the year 2000 The acute toxicity of paracetamol (acetaminophen) in man and experimental animals is due to its dose-dependent metabolic profile. 

Increases in in vivo lipid peroxidation (pentane exhalation) and serum glutamate pyruvate transaminase (SGPT) activity associated with carbon tetrachloride dosing of rats were decreased 50% with Cu(IIX3,5-DIPS)2 treatment whether the animals were fasted or fed [703]. Mice given acetaminophen and treated with Cu(II)(3,5-DIPS)2 were not studied with regard to the prevention of lipid peroxidation, but treatment with Cu(II)(3,5-DIPS)2 did inhibit the elevation in SGPT activity caused by acetaminophen [703]. 

Acetaminophen (paracetamol) is a commonly used analgesic which is hepatotoxic at high doses in humans and in laboratory animals. Toxicity is believed to be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine which binds to protein thiols as 3-(cystein-S-yl)acetaminophen adducts. Ultrasensitive immimoassays for 3-(with parallel elevations in serum adducts and serum levels of the liver-specific transaminase ALT. This suggested that the serum adducts were of hepatic origin and could be monitored as a biomarker of acetaminophen toxicity. Analysis of serum samples from acetaminophen overdose patients demonstrated a positive correlation between immunochemically detectable serum adducts and hepatotoxicity. 

In relation to the administration of medicines for animals, the pharmacological differences and local laws have to be observed. The pharmacokinetics of every active substance is different in each species. For anunals, especially cats, the toxic concentration of many human medicines is lower than the therapeutic dose in humans due to differences in metabolism of medicines. For example, in cats, the administratirm of acetaminophen (paracetamol) very quickly leads to intoxication with methemoglobin formation, anemia, hemoglobinuria and liver damage, as they may metabolise the medicine poorly. 

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