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Jung, Nicole (2008): Zum Einfluss repetitiv duodenal applizierter Aktivkohlegaben auf die Elimination von intravenös verabreichtem Paracetamol (N-Acetyl-para-aminophenol). Dissertation, LMU München: Faculty of Veterinary Medicine
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Abstract

Influence of repetitive duodenal application of activated charcoal on the elimination of the elimination of intravenously applied acetaminophen (N-Acetyl-para-aminophenol) The influence of the repeated administration of activated charcoal on elimination of intravenously injected acetaminophen was investigated in an in-vivo model of anaesthetized rats. 40 rats were randomized and divided into four groups of 10 animals, respectively. Concentration of 14C-marked acetaminophen and its metabolites was measured in plasma, urine and small intestine irrigation samples of all animals. To measure the influence of activated charcoal on elimination of acetaminophen, the small intestine of one half of the animals (n=20) was perfused with activated charcoal dissolved in polyethylene glycol (PEG) (= gastrointestinal dialysis), the small intestine of the other half (n=20) was perfused just with PEG. In order to answer the question whether activated charcoal interrupts enterohepatic circulation, half of the rats treated with activated charcoal and half of the PEG-treated animals (n=10, respectively) were subject to bile duct cannulation; the externalized bile was then quantified for acetaminophen. During a testing period of 3.5 hours, in the ileal effluent of animals with physiological bile flow, we detected ca. 20% of the dose administered originally; in the animals subject to cannulation, we found about 7%. 13% of acetaminophen and metabolites were found in the externalized bile. Activated charcoal did not influence the exsorption of acetaminophen into the small intestine. Terminal half-life in blood ranged from 35-51 minutes, there was no statistically significant difference between the groups (P=0.152). Neither did the Area under curve (AUC) – ranging from 2.6 to 3.3 g/min./l. – show significant variation between groups (P=0.392). Concentration of acetaminophen in liver and kidney samples, which were removed post mortem, was very low, ranging from 0.02 to 0.6% of the dose originally administered. Excretion of acetaminophen into urine varied widely (31-56%), correlating with diuresis. The absence of an effect of activated charcoal on elimination of acetaminophen and metabolites may have been caused by exsorption of insufficient amounts into the intestinal lumen.