文章基本信息

标题：Modulation of the Pharmacokinetics of 5'-Deoxy-5-fluorouridine and 5-Fluorouracil in Rats by Oral Co-administration of Acyclothymidine
本地全文：下载
作者：Akinobu HAMADA ; Shoji FUKUSHIMA ; Mineo SANEYOSHI 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：1996
卷号：19
期号：5
页码：729-732
DOI：10.1248/bpb.19.729
出版社：The Pharmaceutical Society of Japan
摘要：The effect of an inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), acyclothymidine (AcyT), on the pharmacokinetics of 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU) was investigated in an oral co-administration of 5'-DFUR and AcyT in rats. AcyT increased the maximal plasma concentration (C_max) and apparent absorption rate constant (k_a) of 5'-DFUR, as expected, but the increase in AUC (area under the curve) was not significant. It was expected that AcyT would only inhibit the phosphorolytic degradation of 5'-DFUR to 5-FU, but the effect was more evident on the pharmacokinetic parameters of 5-FU than on those of 5'-DFUR. AcyT also increased AUC and C_max of 5-FU when orally co-administered with 5-FU. An inhibitory effect of AcyT on the enzymatic degradation of 5-FU in rat liver and intestinal extract was investigated. AcyT inhibited the degradation in intestinal extract but not in the liver. The result suggests that orally administered AcyT affects the pharmacokinetics of 5-FU partly by inhibiting 5-FU degradation in the process of intestinal absorption as well as by acting as an inhibitor of PyNPase.
关键词：5'-deoxy-5-fluorouridine;5-fluorouracil;acyclothymidine;pyrimidine nucleoside phosphorylase