Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan.
Biol Pharm Bull. 2013;36(6):907-16. doi: 10.1248/bpb.b12-00819. Epub 2013 Apr 11.
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.
我们研究了血浆二氢尿嘧啶/尿嘧啶（UH2/Ura）比值与大肠癌（CRC）大鼠肝二氢嘧啶脱氢酶（DPD）活性的可能替代生物标志物和 5-氟尿嘧啶（5-FU）治疗效果之间的相关性。使用 1,2-二甲基肼诱导的 CRC 大鼠中 DPD 的昼夜变化进行了 5-FU 药代动力学和药效学研究。通过将 5-FU 治疗后的肿瘤体积与治疗前的血浆 UH2/Ura 作图，我们推断出线性关系（r(2)=0.988）。由 DPD 活性变化引起的 5-FU 浓度波动影响肿瘤体积。在接受适当剂量方案的 CRC 患者中，血浆 UH2/Ura 可能是预测 5-FU 治疗效果、肿瘤生长和 5-FU 剂量的间接生物标志物。
