Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Regular Articles
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
Shinji KobuchiYukako ItoKae OkadaKazuki ImotoShota KuwanoKanji Takada
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2013 Volume 36 Issue 6 Pages 907-916

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Abstract

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 (r2=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.

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© 2013 The Pharmaceutical Society of Japan
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