Metabolic disposition of 6-ethyl-3-(1H-tetrazol-5-yl)-chromone, a new antiallergic agent, in the rat, guinea-pig, rabbit, dog and monkey.
1. [14C]Ethyltetrazolylchromone ([14C]ETC) was promptly absorbed from the rat small intestine by the portal route. 2. The maximum plasma concn. of unchanged drug after oral administration (10 mg/kg) was highest in dogs (456 microgram/ml), followed by monkeys (287 microgram/ml), guinea-pigs (146 microgram/ml) and rats (55 microgram/ml), and lowest in rabbits (09 microgram/ml). The half-life of the drug in plasma varied with the species, ranging from 13 to 133 h. The drug was highly bound to plasma protein. In dogs and rats, the plasma 14C was predominantly the unchanged drug, whereas in guinea-pigs, rabbits and monkeys it was mainly metabolites. 3. At 10 min after oral administration of the drug to rats there was a wide distribution of the 14C in the tissues. At this time, the 14C concn. were the highest in stomach, followed by kidney, liver, plasma, heart and lung, and lowest in brain. 4. Almost all administered 14C was eliminated from the body in 72 h. The major route of excretion was via the urine except with guinea-pigs, in which animal the 14C was almost equally divided between urine and faeces. 5. only trace amounts of the unchanged drug were found in urine and bile. The major urinary metabolites were as follows: I (1-hydroxyethyl ETC), II (acetyl ETC), III (IIIa, 2-hydroxyethyl ETC) and IV (1,2-dihydroxyethyl ETC) in rats, I and VI (5-carboxymethylsalicylic acid) in guinea-pigs, I, III (IIIb, carboxymethyl ETC) and VII (ETC-N-1-glucuronide) in rabbits, I and VII in dogs, and I and IV in monkeys.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002850:Chromatography, Gel; D002867:Chromones / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005746:Gastric Emptying / Q000187:drug effects; D006168:Guinea Pigs; D000882:Haplorhini; D006967:Hypersensitivity / Q000188:drug therapy*; D007408:Intestinal Absorption; D008252:Macaca fascicularis; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution
D001798:Blood Proteins; D002867:Chromones; D013777:Tetrazoles