文章基本信息
- 标题：Pre-therapeutic Assessment of Plasma Dihydrouracil/Uracil Ratio for Predicting the Pharmacokinetic Parameters of 5-Fluorouracil and Tumor Growth in a Rat Model of Colorectal Cancer
- 本地全文：下载
- 作者：Shinji Kobuchi ; Yukako Ito ; Kae Okada 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：2013
- 卷号：36
- 期号：6
- 页码：907-916
- DOI：10.1248/bpb.b12-00819
- 出版社：The Pharmaceutical Society of Japan
- 摘要：
We investigated the correlation between plasma ratio of dihydrouracil/uracil (UH2/Ura), a possible surrogate biomarker of hepatic dihydropyrimidine dehydrogenase (DPD) activity, and 5-fluorouracil (5-FU) treatment efficacy in rats with colorectal cancer (CRC). 5-FU pharmacokinetic and pharmacodynamic studies were performed using DPD circadian variation in rats with 1,2-dimethylhydrazine-induced CRC. By plotting tumor volume after 5-FU treatment against pre-therapeutic plasma UH2/Ura, we inferred a linear relationship ( r 2=0.988). 5-FU concentration fluctuations induced by DPD activity variation affected tumor volume. In CRC patients receiving proper dosing regimens, plasma UH2/Ura could be an indirect biomarker for predicting 5-FU treatment efficacy, tumor growth, and 5-FU doses.
- 关键词：pharmacokinetics; biomarker; dihydropyrimidine dehydrogenase; anti-cancer agent
