研究代谢和性格的新类维生素a 4 - [(5、6、7 8-tetrahydro-5 5, 8日8-tetramethyl-2-naphthyl)[氨基甲酰)苯甲酸。4日交流:吸收、代谢、排泄和血浆蛋白结合在不同的动物和人。

文章的细节

引用 复制到剪贴板

Mizojiri K,冈H, Sugeno K,岬,Ito M, Kominami G, Esumi Y,苗M,原田T,塞其H,稻叶型

Arzneimittelforschung。1997年3月,47 (3):259 - 69。

PubMed ID

9105544 (在PubMed

]

文摘

4 - [(5、6、7,8-Tetrahydro-5 5 8日8-tetramethyl-2-naphthyl)[氨基甲酰)苯甲酸(中科院94497-51-5,- 80)是一种新的合成维生素a已被证明有一个强有力的局部antipsoriatic活动。Pharmaco-kinetic资料研究了am - 80在狗、老鼠和兔子后经皮或皮下管理14 c - am - 80。血浆蛋白结合14 c - am - 80也研究了老鼠,狗和人类。局部应用后14 c-labeled am - 80年由闭塞的选矿技术1毫克的剂量c-am-80/1,000 14毫克/公斤的香膏,血液和等离子体辐射水平低于检出限在中性皮肤狗。在正常皮肤老鼠和兔子,等离子体辐射达到8 h (eq. 40.8 ng / ml),在12 h (eq. 34.0 ng / ml)应用程序后,分别。经皮吸收的14 c - am - 80年不到2%的剂量为狗,兔子,老鼠为23%,34%。皮下后政府的剂量1毫克/公斤老鼠,狗和兔子,等离子体辐射水平达到1,4,4 h后加药浓度为614.0,902.9和757.7 ng eq. /毫升,然后拒绝半衰期为2.4,7.2和4.1 h,分别。尿和粪便排泄的剂量皮下后放射性管理1毫克/公斤是3.5和94.7%剂量的狗,老鼠73.2%和27.0和43.5 45.6%,兔子。可能胃肠道分泌,这可能会导致排泄粪便,建议从结果bile-duct-cannulated狗。不变am - 80年出现在大量的等离子体和胆汁或粪便的动物物种测试除了大鼠胆汁,am - 80的形式主要是检测其牛磺酸共轭(M-6)。 Hydroxylation of Am-80 to yield 7-hydroxy-Am-80 (M-4) and 6-hydroxy-Am-80 (M-3), which lead to the formation of 6-oxo-Am-80 (M-5), were commonly observed in all animal species. Taurine conjugation reaction of unchanged Am-80 and hydroxy-Am-80 (to form M-6 and both M-1 and M-2, respectively) was distinct in rats and dogs, but, hardly detected in mice and rabbits. The presence of tetrahydro-tetramethyl-naphtylamine (TTNA) was most marked in mice, followed by rabbits and rats, but it was almost absent in dogs. HPLC-RIA analysis of human samples obtained from the phase II and phase III clinical trials of Am-80 ointment suggested that fecal excretion was the major elimination route, and that hydroxylation and taurine conjugation reaction of unchanged and hydroxy-Am-80 also occurred. Unchanged Am-80 was predominant in human plasma as compared with metabolites M-1 to M-6. In vitro binding of 14C-Am-80 to the plasma protein was found to be more than 99% in rats, dogs and humans. In vivo plasma protein binding of 14C-Am-80 and/or its radioactive metabolites was also found to be more than 98% in rats and dogs after subcutaneous administration of 14C-Am-80. In both dogs and humans, in vitro. 14C-Am-80 appeared to be bound predominantly to serum albumin. The binding of 14C-Am-80 to human serum albumin was scarcely affected in the presence of diazepam, digitoxin or warfarin, indicating that there are no specific binding sites for Am-80 on serum albumin.

DrugBank数据引用了这篇文章

药物: Tamibarotene