去氧氟尿苷及其代谢物在肿瘤病人体内药代动力学研究

the Pharmacokinetics of 5'-Deoxy-5-Fluridine (5'-DFUR) and Its MajorMetabolite 5-Fluorourcail (5-FU) in Tumor Patients

目的:主要研究了去氧氟尿苷(5’－deoxy－5－fluridine)及其主要代谢物5－氟尿嘧啶在肿瘤病人体内的药代动力学特征。方法:肿瘤病人口服800mg去氧氟尿苷胶囊,采用高效液相色谱法(HPLC)分别测定肿瘤病人体内中的去氧氟尿苷和其主要代谢物5－氟尿嘧啶的血药浓度。结果:肿瘤病人体内去氧氟尿苷的血药浓度－时间曲线下面积AUC0-∞为:6.45±1.71mg·h·L-1末端相消除半衰期t(1/2)为:0.65±0.23h,峰时间和峰浓度分别为:1.00±0.37h和5.11±1.36mg·L-1。5－氟尿嘧啶的血药浓度－时间曲线下面积AUC0-∞为:222.7±86.3μg·h·L-1,末段消除相的半衰期t(1/2)为:0.65±0.50h,峰时间tmax和峰浓度Cmax分别为的0.93±0.26h和199.11±89.14μg·L-1。比较不同肿瘤病人的药动学参数,胃癌病人对去氧氟尿苷的吸收与肝癌和结肠癌病人有差异,去氧氟尿苷在不同肿瘤病人体内代谢成5－氟尿嘧啶未见明显差异。结论:去氧氟尿苷在三种肿瘤病人体内的吸收可能有差异,其主要药代动力学特征没见明显改变。

OBJECTIVE: The pharmacokinetics of 5'-deoxy-5-fluridine (5'-DFUR)and its major metabolite 5-fluorourcail (5-FU) was investigated in ten tumor patientsafter oral administration of 800mg 5'-DFUR capsules. METHODS:The 5'-DFURand 5-FU plasma concentration was measured by HPLC. RESULTS:The area underconcentration of 5'-DFUR was 6.45±l.7lmg.h.L-1,The half life of 5'-DFUR was0.65±0.23h, The peak concentration of 5'-DFUR was 5.ll±l.36mg.L-1, arrivedat l.00±0.37h. The area under concentration of 5-FU was 222.7±86.3μg.h.L-1,The half life of 5-FU was 0.65±0.50h, The peak concentration of 5-FU was l99.ll±89.l4μg.L-1, arrived at 0.93±0.26h. CONCUSION: The absorption of 5'-DFUR in gastric carcinoma patients was different with the other patients. the areaunder concentration of 5'-DFUR and it half-life were no difference among tenpatients.