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
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概要
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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.
- 公益社団法人 日本薬学会の論文
著者
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ITO Yukako
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Takada Kanji
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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Imoto Kazuki
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Kobuchi Shinji
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Okada Kae
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Kuwano Shota
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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