Kucharczyk N, Ballard F, Yang J, Myers G, Sofia R D
Arch Int Pharmacodyn Ther. 1979 Jun;239(2):180-94.
3-Methyl-2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one was readily absorbed, metabolized and eliminated in rat, dog, monkey and man. The radioactivity elimination after i.v. or p.o. administration of W-2451-14C in rats was biphasic with corresponding half-lives of 1.8 and 8.7 hours. Plasma half-lives of W-2451 in the dog, rhesus monkey and man were 1.4, 1.2 and 3.2 hours, respectively. In the rat, excretion via the urine was predominant, no significant accumulation in tissue occurred. The only major metabolite found in rat and dog urine, rat plasma and in the rat liver 9000 g supernatant fraction was the 3-hydroxy derivative of the drug. The unsaturated compound with the double bond in the 2,3-position and other hydroxylated metabolites were also present. Very little free or conjugated anthranilic acid and 3-(o-carboxy-phenylimino)-4-methylisoxazolidine were found.
3-甲基-2,3-二氢-9H-异恶唑并[3,2-b]喹唑啉-9-酮在大鼠、狗、猴和人体内易于吸收、代谢和消除。大鼠静脉注射或口服W-2451-¹⁴C后的放射性消除呈双相，相应半衰期分别为1.8小时和8.7小时。W-2451在狗、恒河猴和人体内的血浆半衰期分别为1.4小时、1.2小时和3.2小时。在大鼠体内，主要通过尿液排泄，组织中无明显蓄积。在大鼠和狗的尿液、大鼠血浆以及大鼠肝脏9000g上清液组分中发现的唯一主要代谢物是该药物的3-羟基衍生物。还存在2,3位带有双键的不饱和化合物和其他羟基化代谢物。发现游离或结合的邻氨基苯甲酸以及3-(邻羧基苯基亚氨基)-4-甲基异恶唑烷极少。
