文章基本信息

标题：An in Vivo Approach for Globally Estimating the Drug Flow between Blood and Tissue for Nafamostat Mesilate: the Main Hydrolysis Site Determination in Human
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作者：Yan-Guang Cao ; Yuan-Cheng Chen ; Kun Hao 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：11
页码：1985-1989
DOI：10.1248/bpb.31.1985
出版社：The Pharmaceutical Society of Japan
摘要：Nafamostat mesilate, an ester drug with extensive hydrolysis in vivo , exhibits species difference in the relative contribution for its hydrolysis in blood and tissues. For the rat, the main hydrolysis site may be blood and human may be tissue (mainly by liver). The paper gave in vivo evidence that human tissue may give more contribution for its hydrolysis. In the initial phase of drug administration, the drug accumulating level in tissue was low; the efflux fraction from tissue into blood can be ignorable comparing with the drug influx into tissue. Based on urine and plasma metabolite analysis, we concluded that in the initial phase almost all the drug hydrolysis in blood was excreted into urine. Then according to the initial urine metabolite analysis, we can estimate the drug hydrolysis rate in blood. The rate of drug diffusion from blood into tissues can be deduced based on the mass balance analysis of the initial blood drug. With the estimated rate constants, the drug efflux from tissues into blood was calculated according to equation: OF _T-B (efflux from tissues) = OF _B-U (blood hydrolysis fraction)+ OF _B-T (influx into tissues)− D _B (hydrolysis in blood). The net flow (influent flux minus effluent flux) represented the drug hydrolysis fraction in tissue. As the result indicated, in human about 20% drug administrated was hydrolyzed in blood and nearly 80% in tissues. The relative hydrolysis fraction indicated that the main hydrolysis site in human body may locate in tissue, which was different to rats.
关键词：nafamostat mesilate;in vivo approach;hydrolysis site;drug flow;globally estimating