Biliary excretion and enterohepatic circulation of paracetamol in the rat. 1983

C P Siegers, and K Rozman, and C D Klaassen

Within 8 h after i.v. administration of paracetamol (100 mg/kg) to rats, 28.7% was excreted into bile; 1.2% dose as unchanged drug, 14.3% as the glucuronide, 8.2% as the sulphate, 4.7% as the glutathione conjugate, 0.32% as the mercapturate. Rats with cannulated bile-ducts excreted 62.8% dose in the urine in 8 h compared with 83.5% in sham-operated rats. Metabolites in urine were paracetamol sulphate (63.2%), the glucuronide (12.1%), unchanged paracetamol (7%), and the mercapturate (1.2%). Bile containing paracetamol and its conjugates was infused into the duodenum and within 8 h 45.3% was excreted (5.6% in bile and 39.7% in urine). In rats not subjected to surgery, 91.3% dose (100 mg/kg, i.v.) was excreted in urine in 24 h. However, in rats treated twice with activated charcoal or cholestyramine (2 X 1 g/kg orally), urine excretion was decreased to 72.8 and 59.3% dose, respectively. These results indicate the enterohepatic circulation of paracetamol and its metabolites in the rat.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004386 Duodenum The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers. Duodenums
D004764 Enterohepatic Circulation Recycling through liver by excretion in bile, reabsorption from intestines (INTESTINAL REABSORPTION) into portal circulation, passage back into liver, and re-excretion in bile. Circulation, Enterohepatic,Entero-Hepatic Circulation,Circulation, Entero-Hepatic,Circulations, Entero-Hepatic,Circulations, Enterohepatic,Entero Hepatic Circulation,Entero-Hepatic Circulations,Enterohepatic Circulations
D000082 Acetaminophen Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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