文章基本信息

标题：DETERMINATION OF PLASMA TRIMETHADIONE AND ITS METABOLITE IN CARBON TETRACHLORIDE-INTOXICATED RATLIVER : A USEFUL TOOL FOR ESTIMATION OF HEPATIC DRUGMETABOLIZING CAPACITY
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作者：EINOSUKE TANAKA ; HARUKI KINOSHITA ; TAKEMI YOSHIDA 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：1981
卷号：4
期号：12
页码：961-967
DOI：10.1248/bpb1978.4.961
出版社：The Pharmaceutical Society of Japan
摘要：1. The relationship between the plasma concentration ratio of 5, 5-dimethyl-2, 4-oxazolidinedione (DMO) to trimethadione (TMO) and cytochrome P-450 dependent drug-metabolizing enzyme activities after administration of TMO to rats pretreated with different dose levels of carbon tetrachloride (CCl₄) was investigated. 2. Pretreatment of rats with different dose levels of CCl₄ resulted in a prolongation of TMO half-life, an increase of the area under the curve (AUC), and a decrease of clearance, but the apparent volume of distribution (V_d) was not significantly decreased. 3. Depending on the extent of liver-injury by CCl₄, there was a good correlation between the ratio of DMO to TMO in plasma and hepatic cytochrome P-450 dependent drug-metabolizing enzyme activities such as cytochrome P-450 content (r=0.796 at 1 h, r=0.849 at 2 h), aminopyrine N-demethylase activity (r=0.877 at 1 h, r=0.905 at 2 h), TMO N-demethylase activity (r=0.876 at 1 h, r=0.928 at 2 h) and aniline hydroxylase activity (r=0.900 at 1 h, r=0.936 at 2 h). 4. These results, together with the previous findings, indicate that determination of the plasma levels of TMO and DMO might be a useful tool as an index of drugmetabolizing capacity of rat livers.
关键词：liver injury