Naltrexone-3-salicylate (a Prodrug of Naltrexone): Synthesis and Pharmacokinetics in Dogs
Naltrexone-3-salicylate (a Prodrug of Naltrexone): Synthesis and Pharmacokinetics in Dogs
复制标题
3-水杨酸纳曲酮（纳曲酮前药）：合成和在狗中的药代动力学
DOI：
10.1023/a:1015944302567
复制
发表时间：
1988
影响因子：
3.7
通讯作者：
E. Shefter
中科院分区：
文献类型：
--
作者：
M. Hussain;E. Shefter
3-水杨酸纳曲酮 (3) 是纳曲酮 (1) 的前药，通过简单的程序由 3-乙酰水杨酸纳曲酮 (2) 制备。发现 3 的血浆（狗和人）水解半衰期约为 30 分钟。先前显示化合物 2 在狗和人血浆中水解，先快速脱乙酰化至 3，然后缓慢水解 3 至 1（t1/2，约 30 分钟）。给狗口服3后，口服纳曲酮的生物利用度大大提高（〜30倍），与口服2后观察到的改善相似。口服3后，狗体内纳曲酮的半衰期与口服2后观察到的相似（〜1小时）。
Naltrexone-3-salicylate (3), a prodrug of naltrexone (1), was prepared by a simple procedure from naltrexone-3-acetylsalicylate (2). The plasma (dog and human) hydrolysis half-life of 3 was found to be approximately 30 min. Compound 2 was previously shown to hydrolyze in dog and human plasma with a fast deacetylation step to 3, followed by slower hydrolysis of 3 to 1 (t1/2, ∼30 min). Oral naltrexone bioavailability was greatly improved (∼30-fold) after oral administration of 3 to dogs, similar to the improvement observed after oral administration of 2. The half-life of naltrexone in dogs after oral administration of 3 was similar to that observed after oral administration of 2 (∼1 hr).