Improving the ex vivo stability of drug ester compounds in rat and dog serum: Inhibition of the specific esterases and implications on their identity

In drug development, it has been noticed that some drug compounds, especially esters, are unstable in serum samples ex vivo. This can lead to a substantial underestimation of the actual drug concentration.     

胆酸螯合剂类降胆固醇药物研究进展

介绍多种类型胆酸螯合剂(包括带烷基季铵盐、苄基季铵盐、咪唑(?)盐活性基团的阴离子交换树脂)、在聚合物骨架和官能团间引入间隔基团的树脂以及若干新类型骨架的树脂的制备、结构特征、胆酸结合活性、降胆固醇活性等。对树脂吸附胆酸过程中的选择性和位阻作了讨论。     

Effect of colestimide on absorption of unconjugated bile acids in the rat jejunum

BACKGROUND: Colestimide is a newly developed bile acid-binding resin in Japan, but its bile acid-binding properties have not been studied. METHODS: The absorption of unconjugated bile acids (5 mmol/L) in the ligated rat jejunum was compared in the presence and absence of colestimide. Furthermore, bile acid adsorption by colestimide was also studied in vitro. RESULTS: All bile acids were efficiently absorbed in the jejunum and the cumulative absorption during 120 min was 29-63%. The absorption of chenodeoxycholate, lithocholate, deoxycholate and ursodeoxycholate was dose-dependently inhibited by 2.5 and 5 mg colestimide, whereas the absorption of cholate was not inhibited, even in the presence of 5 mg colestimide. Adsorption of bile acids by colestimide in vitro was approximately 60% for chenodeoxycholate, lithocholate, deoxycholate and ursodeoxycholate, whereas the adsorption of cholate was low (16%). CONCLUSIONS: Jejunal absorption of ursodeoxycholate was inhibited by colestimide to a similar extent as other dihydroxy bile acids, whereas that of cholate was not inhibited under the same conditions.