文章基本信息

标题：Pharmacokinetic Interaction of Zonisamide in Rats. Effect of Other Antiepileptics on Zonisamide
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作者：Masahiko KIMURA ; Naomi TANAKA ; Yasuhiro KIMURA 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：1992
卷号：15
期号：11
页码：631-639
DOI：10.1248/bpb1978.15.631
出版社：The Pharmaceutical Society of Japan
摘要：The pharmacokinetics of zonisamide (ZNS) and the effects of phenobarbital (PB), valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) on ZNS kinetics were investigated in rats. The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS. ZNS showed a linear disposition kinetics after oral administration of ZNS within the dose examined. Moreover, the pharmacokinetic behaviors of ZNS were not altered after multiple dosing. The decreased t_1/2 value of ZNS by PB or CBZ pretreatment and the increased Vd/F value of ZNS by VPA pretreatment were observed, although it showed no marked effect of PHT on ZNS kinetics. The enhanced metabolism of ZNS was observed by PB or CBZ pretreatmtent from an in vitro metabolism study. The serum protein binding and erythrocyte distribution of ZNS showed no significant change in the presence of other antiepileptics in vitro. These results indicate that the decreased t_1/2 value of ZNS is attributable to the enzyme inducing effect of PB or CBZ, and that neither protein binding nor erythrocyte distribution of ZNS could be the reason for the increased Vd/F value of ZNS by VPA coadministration.
关键词：metabolism