Metabolic disposition of 6-chloro-5-cyclohexyl-1-indancarboxylic acid (TAI-284), a new non-steroidal anti-inflammatory agent, in rhesus monkeys. 1977

S Tanayama, and Y Kanai

1. After oral administration of 6-chloro-5-cyclohexyl-1-indan[14C]carboxylic acid (TAI-284) to rhesus monkeys, the plasma concn. reached a plateau at 2 h, which persisted for 4 h and then declined with an approximate half-life of 24 h. More than 92% of the plasma radioactivity was derived from unchanged TAI-284. The plasma concn. of the ulcerogenic metabolite, 6-chloro-5-(cis-3'-hydroxycyclohexyl)-1-indancarboxylic acid (metabolite IIb), was much lower in monkeys than in rats. 2. In monkeys, elimination of the ingested radioactivity was complete in 96 h, the excretion being almost equally divided between urine and faeces. This excretory pattern was similar to that in rats. The major urinary metabolites in monkeys were TAI-284, 6-chloro-5-(trans-4'-hydroxycyclohexyl)-1-indancarboxylic acid (metablite III) and glucuronides of TAI-284 and its oxo or hydroxy derivatives (metabolite VI), whereas those in rats were dihydroxy derivatives of TAI-284 (metabolite V) and VI. Unchanged TAI-284 accounted for only a small part of the faecal radioactivity in monkeys and rats. 3. Both in monkeys and rats, some of the dose of radioactivity was excreted in bile to enter into entero-hepatic cycling. Biliary excretion of metabolite IIb was markedly smaller in monkeys than in rats. 4. These metabolic findings are discussed in relation to the variation in the TAI-284-induced intestinal ulceration between monkeys and rats.

UI MeSH Term Description Entries
D007189 Indans Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES. Indanones
D007192 Indenes A family of fused-ring hydrocarbons isolated from coal tar that act as intermediates in various chemical reactions and are used in the production of coumarone-indene resins.
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008297 Male Males
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
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
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
D000882 Haplorhini A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes). Anthropoidea,Monkeys,Anthropoids,Monkey
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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