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新型抗过敏药6-乙基-3-(1H-四氮唑-5-基)-色酮在大鼠、豚鼠、兔、犬和猴体内的代谢情况

Metabolic disposition of 6-ethyl-3-(1H-tetrazol-5-yl)-chromone, a new antiallergic agent, in the rat, guinea-pig, rabbit, dog and monkey.

作者信息

Kanai Y, Nakai Y, Nakajima N, Tanayama S

出版信息

Xenobiotica. 1979 Jan;9(1):33-50. doi: 10.3109/00498257909034702.

DOI:10.3109/00498257909034702
PMID:104449
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 (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.
摘要
  1. [14C]乙基四氮唑基色酮([14C]ETC)经门静脉途径迅速从大鼠小肠吸收。2. 口服给药(10毫克/千克)后,未变化药物的最高血浆浓度在犬中最高(456微克/毫升),其次是猴(287微克/毫升)、豚鼠(146微克/毫升)和大鼠(55微克/毫升),在兔中最低(09微克/毫升)。药物在血浆中的半衰期随物种而异,范围为13至133小时。该药物与血浆蛋白高度结合。在犬和大鼠中,血浆中的14C主要是未变化的药物,而在豚鼠、兔和猴中主要是代谢产物。3. 给大鼠口服药物10分钟后,14C在组织中分布广泛。此时,14C浓度在胃中最高,其次是肾、肝、血浆、心脏和肺,在脑中最低。4. 几乎所有给药的14C在72小时内从体内消除。排泄的主要途径是通过尿液,但豚鼠除外,在豚鼠中,14C在尿液和粪便中的分布几乎相等。5. 在尿液和胆汁中仅发现痕量的未变化药物。主要的尿代谢产物如下:大鼠中的I(1-羟乙基ETC)、II(乙酰基ETC)、III(IIIa,2-羟乙基ETC)和IV(1,2-二羟乙基ETC),豚鼠中的I和VI(5-羧甲基水杨酸),兔中的I、III(IIIb,羧甲基ETC)和VII(ETC-N-1-葡萄糖醛酸苷),犬中的I和VII,以及猴中的I和IV。

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