【摘要】 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。更多还原

【Abstract】 Objective:While 5 FU was administered during day or night, its stead steady plasma concentration (Css) and toxicity of the regimens were compared so as to find out more effective administration of 5FU . Methods:A tolal of 18 patients randomly received CF plus 5 FU during day or night. 5 FU 1000 mg·(m 2·d) -1 was given by 8 hours continuous intravenously infusion ( IV ) for 5 days (d1～5 ), leucovorion 100 mg was administered after 5 FU infusion at 0,4,8 hour, together with carboplatin 300～350 mg/m 2,was administred IV on d6. Using HPLC method, plasma concentrationg of 5 FU were detected in 12 patients at 2,4,6,8 hour after 5 FU infusion. Results:Pharmacokinetics data showed although 5 FU was continuously infused at a constant rate, the Css of this drug varied in a circadian rhythmic manner, with maximal values occuring at 1AM. Area under concentration curve (AUC) of 5 FU at night was significantly higher than that during day. While CF flus 5 FU were administered at night, close positive correlation between 5 FU pharmacokinetics data (maximum Css, AUC) and the risk of mucositis were found. But in the daytime, these relationship was insignificant. No difference in toxicity was observed while CF flus 5 FU were administered during day or night at constant rate. Conclusion:It is suggested that toxicity of 5 FU may be related to its plasma concentration and sensitivity of target tissue. The optimal administration of 5 FU should be continuous IV, with peak between 3AM to 5AM,because it is helpful to avoid administration of 5 FU during its maximum plasma concentration and active DNA synthesis of oral mucosa.更多还原