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目的 :探讨夜间、白天恒速静滴 5 氟尿嘧啶 ( 5 fluorouracil,5 FU)时 ,其稳态血药浓度及毒性的时辰变化 ,为制定适合我国患者的 5 FU给药方案提供依据。方法 :文应用高效液相色谱法测定 5 FU血药浓度。 18例晚期鼻咽癌患者前后两个疗程随机接受CF、5 FU白天及夜间化疗 5天 ,5 FU 10 0 0mg·(m2 ·d) - 1 连续 8小时恒速静滴 ,CF 10 0mg在 5 FU静滴第 0、4、8小时 ,分别三次静推 ,卡铂 3 0 0～ 3 5 0mg/m2 ,第 6日静滴。对其中 12例患者在每疗程 5 FU静滴后第 2、4、6、8小时取静脉血测定血药浓度。结果 :恒速静滴 5 FU其稳态血药浓度 (Css)存在明显昼夜节律波动 ,高峰在 1AM ,夜间药时曲线下面积 (AUC)高于白天。夜间静滴 ,本方案的主要剂量限制性毒性口腔粘膜炎 ,与 5 FU高峰血药浓度、AUC相关 ,但在白天静滴 ,这种相关性不明显。 5 FU白天、夜间恒速静滴 ,该方案毒副反应无差异。结论 :5 FU毒性可能与其血药浓度及靶组织敏感性等因素有关 ,推测 5 FU较合理给药方式应是 2 4小时连续静滴 ,高峰滴速在 3AM 5AM ,因为这种给药方式避免了在高峰血药浓度及口腔粘膜细胞DNA合成活跃的时间给予较高浓度的 5 FU。
OBJECTIVE: To investigate the time course of steady-state plasma concentration and toxicity of 5-fluorouracil (5 FU) intravenous drip during the daytime and the daytime in order to provide a basis for formulating 5 FU regimen suitable for Chinese patients. Methods: The application of high performance liquid chromatography 5 FU blood concentration. 18 patients with advanced nasopharyngeal carcinoma before and after two courses of randomized CF, 5 FU day and night chemotherapy for 5 days, 5 FU 10 0mg · (m2 · d) - 1 for 8 hours continuous infusion of constant velocity CF 10 0mg in 5 FU intravenous infusion 0,4,8 hours, respectively, three times the static push, carboplatin 300 ~ 350mg / m2, intravenous infusion on the 6th. Twelve of these patients were given venous blood at the 2nd, 4th, 6th, and 8th hour after every 5 FU infusion. Results: The steady-state blood concentration (Css) of constant-flow intravenous 5 FU showed significant circadian rhythms with peak at 1 AM and the area under the curve (AUC) at night was higher than that at daytime. Intravenous infusion at night, the main dose-limiting toxic oral mucositis, and 5 FU peak plasma concentration, AUC-related, but intravenous infusion during the day, this correlation is not obvious. 5 FU during the day and night constant infusion rate, the program no difference in side effects. Conclusions: 5 FU toxicity may be related to its plasma concentration and target tissue sensitivity. It is speculated that 5 FU should be administered intravenously 24 hours continuously with a peak drip rate of 3 AM 5 AM because this mode of administration avoids In the peak plasma concentration and oral mucosal DNA synthesis is active at a higher concentration of 5 FU.