In vitro and in vivo study of water-soluble prodrugs of dexanabinol.
In vitro and in vivo study of water-soluble prodrugs of dexanabinol.
复制标题
地塞米诺水溶性前药的体外和体内研究。
DOI：
10.1021/js990098j
复制
发表时间：
1999
影响因子：
3.8
通讯作者：
Prokai,L
中科院分区：
文献类型：
--
作者：
Pop,E;Rachwal,S;Vlasak,J;Biegon,A;Zharikova,A;Prokai,L
Trialkylammonium acetoxymethyl esters of dexanabinol were synthesized and evaluated as water-soluble prodrugs. Syntheses were performed by conventional methods; solubility in water and stability in buffers and human plasma were determined by HPLC, and in vivo tissue distribution studies were performed in a rat model. Most of the new derivatives were soluble in water (∼50 mg/mL). They were relatively stable in water, while rapidly hydrolyzed in human plasma. Distribution studies indicated that peak concentrations of drug both in blood (30 μg/mL) and brain (2 μg/mL) were rapidly (5 min) achieved after iv administration of a selected prodrug to rats. The blood concentration decreased faster than brain levels which were detectable even after 24 h. Some of the examined esters could be further developed as water soluble prodrugs of dexanabinol.
