Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
FALCO Biosystems Ltd, 346, Shimizu-cho, Nijo-agaru, Kawaramachi-dori Nakagyo-ku, Kyoto, 604-0911, Japan.
Sci Rep. 2020 Feb 17;10(1):2711. doi: 10.1038/s41598-020-59648-2.
Capecitabine is selectively converted from 5'-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection.
卡培他滨在肿瘤组织中由胸苷磷酸化酶(TP)选择性地从 5'-DFUR 转化为 5-氟尿嘧啶(5-FU)。我们研究了将胸苷磷酸化酶抑制剂 5-硝基尿嘧啶(5-NU)添加到血液样本中,以精确测量血浆 5-FU 浓度。在给予卡培他滨后测量血浆 5-FU 浓度。在给予卡培他滨后 1 或 2 小时获得两个样本,并向每个样本对中的一个添加 5-NU。将样本在室温或 4°C 下储存,并在立即或 1.5 或 3 小时后测量 5-FU 浓度。室温下的平均血浆 5-FU 浓度明显高于 4°C(p<0.001)。在没有 5-NU 的情况下,5-FU 浓度明显高于有 5-NU 的情况(p<0.001)。在没有 5-NU 的情况下,5-FU 浓度的变化更大,与基线相比达到最大值的 190%。发现温度和 5-NU 条件之间存在显著的相互作用(p<0.001)。在室温下,5-NU 存在或不存在时的差异大于冷藏条件下的差异。卡培他滨给药后 5-FU 血浆浓度随时间、温度和 5-NU 的存在与否而变化。这表明,5-FU 浓度在采血后根据储存条件而变化。