Metabolic disposition of 14C-labelled Brown HT in the rat, mouse and guinea-pig. 1987

J C Phillips, and D Mendis, and I F Gaunt
British Industrial Biological Research Association, Carshalton, Surrey, England.

The absorption, metabolism, tissue distribution and excretion of 14C-labelled Brown HT has been studied in the rat, mouse and guinea-pig. Following administration of a single oral dose of either 50 or 250 mg Brown HT/kg, substantially all of the dose was excreted in the urine and faeces within 72 hr, with the majority (more than 80%) being accounted for in the faeces. A significant difference in urinary excretion of radioactivity was seen between male and female rats, as well as clear species differences at the two dose levels used. In all species studied, naphthionic acid was the major urinary metabolite, whereas in the faeces naphthionic acid, trace quantities of unchanged dye and at least two unidentified metabolites were found. Pregnant rats eliminated a single oral dose of 14C-labelled colouring at a rate similar to that in non-pregnant females, but some retention of radioactivity was found in the foetuses. Radioactivity was present in all tissues of male rats 24 hr after an oral dose of 250 mg 14C-labelled Brown HT/kg, with the highest concentrations in the gastro-intestinal tract, kidney and lymph nodes. Clearance from the gastro-intestinal tract was more rapid than from other tissues, but by day 7, the concentration of radioactivity (less than 0.001% of the dose/g) was similar in all tissues except the kidney and mesenteric lymph nodes. Similar results were obtained with animals pretreated for 21 days with either unlabelled or 14C-labelled Brown HT (250 mg/kg/day) prior to a radioactive dose. For most tissues examined, the concentration of radioactivity was greater with pretreatment than without. These results suggest that despite the rapid reduction and elimination of the major part of an oral dose of Brown HT, some colouring and/or metabolites accumulate in most tissues of male rats during repeated daily administration, but that only in the kidney and mesenteric lymph nodes is the accumulation tissue-specific. The accumulated radioactivity is cleared rapidly from most tissues on cessation of treatment. No significant absorption of either Brown HT, metabolites or subsidiary dyes was detected using isolated loops of small intestine.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008297 Male Males
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D005260 Female Females
D005505 Food Coloring Agents Natural or synthetic dyes used as coloring agents in processed foods. Coloring Agents, Food,Food Colorants,Agents, Food Coloring,Colorants, Food
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
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
D001391 Azo Compounds Organic chemicals where aryl or alkyl groups are joined by two nitrogen atoms through a double bond (R-N Azo Dye,Azo Dyes,Compounds, Azo,Dye, Azo,Dyes, Azo
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
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

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