Assay development for determination of DZ2002, a new reversible SAHH inhibitor, and its acid metabolite DZA in blood and application to rat pharmacokinetic study / 药物分析学报

Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90％–159％. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.

Pharmacodynamics of anti-diarrhea medicine of the compound catechu antidiarrheal ointment / 重庆医学

Objective To observe the gastrointestinal function influence in the compound catechu antidiarrheal ointment when acted on normal and diarrheic mice .Methods The antidiarrheal function of the compound catechu antidiarrheal ointment was ob-served through the mice small intestinal propulsion experiment ,gastric emptying experiment and mice diarrhea situation influence test of senna .Results This ointment could reduce the mice small intestine propulsion rate which significantly restrained the mice small intestine propulsion ;Also it could improve the residual rate of mice stomach contents ,significantly restrained their gastric emptying velocity .Conclusion The compound catechu antidiarrheal ointment has strong and lasting effect on stopping diarrhea .