Metabolic Disposition of 6-Ethyl-3-(1H-tetrazol-5-yl)-chromone, a New Antiallergic Agent, in the Rat, Guinea-pig, Rabbit, Dog and Monkey

Abstract

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 (45.6 μg/ml), followed by monkeys (28.7 μg/ml), guinea-pigs (14.6 μg/ml) and rats (5.5 μg/ml), and lowest in rabbits (0.9 μg/ml). The half-life of the drug in plasma varied with the species, ranging from 1.3 to 13.3 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-glucurcnide) in rabbits, I and VII in dogs, and I and IV in monkeys.