文章基本信息

标题：Inhibition of Theophylline Metabolism by Suplatast and Its Metabolites in Rats
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作者：Makiko Kizawa ; Etsuko Miyamoto ; Shuka Aono 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：2005
卷号：28
期号：6
页码：1061-1065
DOI：10.1248/bpb.28.1061
出版社：The Pharmaceutical Society of Japan
摘要：The inhibitory effect of suplatast (ST), an anti-allergic drug, on theophylline (TP) metabolism was investigated in rats in vivo and in vitro . Intravenous injection of aminophylline (AP) at 10 mg/kg of TP equivalent was performed with or without pretreatment by oral administration of 100 mg/kg of ST 2.5 h prior to AP. In the ST-pretreated group, plasma concentration (Cp), the area under Cp–time profile (AUC) and urinary excretion of TP increased significantly, and urinary excretion of TP metabolites, 1,3-dimethyluric acid (DMU) and 1-methyluric acid (1MU) decreased significantly. Metabolic clearance of DMU (CL_DMU) and that of 1MU (CL_1MU) were remarkably suppressed by ST pretreatment, however, renal clearance (CLr) of TP did not change. To compare the inhibitory effect of ST on TP metabolism with that of its main metabolite (M1) in vivo , a concomitant intravenous injection of AP (10 mg/kg of TP equivalent) with ST or M1 (40 mg/kg of ST equivalent) was carried out. In the M1 group, Cp and AUC of TP increased significantly, and the total body clearance of TP decreased significantly. In contrast, ST did not induce these changes. Then, the inhibitory effect of ST and M1 on TP metabolism in vitro was evaluated using rat-liver microsomes. ST and M1 suppressed DMU formation in a competitively inhibitory manner, and their equilibrium dissociation constants ( K _i) were 822 and 731 μ M , respectively. In conclusion, inhibition of TP metabolism by ST was demonstrated in vivo and in vitro , and the involvement of M1 and/or other metabolites in this drug interaction was suggested.
关键词：theophylline;suplatast;drug interaction;metabolism;rat;microsome