羟基喜素碱片在肿瘤患者体内的绝对生物利用度  

Absolute bioavailability of hydroxycamptothecin tablets in cancer patients

作　　者：李苏[1] 张力[1] 管忠震[1] 詹靖[1] 李玉颜[1] 姜文奇[1] 

机构地区：[1]中山大学肿瘤防治中心心内科,广东广州510060

出　　处：《中国临床药理学杂志》2005年第1期46-49,共4页The Chinese Journal of Clinical Pharmacology

基　　金：广东省卫生厅基金资助项目(A2001042)

摘　　要：目的研究羟基喜树碱(HCPT)在肿瘤患者体内的绝对生物利用度。方法用随机交叉自身对照试验设计,8名肿瘤患者随机等分成2组,先后口服HCPT片剂或静脉注射HCPT针剂,用高效液相-荧光色谱法测定血药浓度。用3P97软件计算主要药代动力学参数,用梯形法计算AUC0→t。结果HCPT注射剂的主要药代动力学参数:Cmax为(2527±627)μg·L-1,t1/2α为(0.39±0.17)h,t1/2β为(4.27±2.25)h,Vc为(5.76±4.8)L,AUC为(2171.60±515.00)μg·h·L-1,CL为(55.25±5.14)L·h-1;HCPT片剂的主要药代动力学参数:Cmax为(127.80±32.90)μg·L-1,tmax为(2.37±0.70)h,tlag为(0.14±0.04)h,ka为(0.29±0.13),t1/2α为(1.73±0.18)h,t1/2β为(6.17±0.32)h,AUC为(693.80±23.50)μg·h·L-1,绝对生物利用度为(31.95±3.4)%。口服吸收符合一级吸收动力学过程,12h浓度大于10μg·L-1。结论HCPT片剂可维持12h有效血药浓度,且较静脉给药,t略呈后移现象,推测可能存在肠、肝循环。Objective To evaluate the absolute bioavailability of hydroxycamptothecin(HCPT) tablets in cancer patients. Methods A paired, crossover design was used. Eight cancer male patients were randomized into 2 groups. Group one first received injectioins, and then followed by tablets. Blood samples were collected at different time spots. Plasma concentration of HCPT was measured by high-performance liquid chromatography and fluorescence spectrophotometry. The pharmacokinetic parameters were measured by 3P97, and AUC 0→t was calculated by trapezoidal rule. Results The major pharmacokinetic parameters of injection were as follow: C max was (2527±627)μg·L -1,t 1/2α was (0.39±0.17) h,t 1/2β was (4.27±2.25)h,V c was (5.76±4.8)L,AUC was (2171.60±515.00)μg·h·L -1, CL was (55.25±5.14)L·h -1. The major pharmacokinetic parameters of tablet were as follow: C max was (127.80±32.90)μg·L -1,t max was (2.37±0.70)h,t lag was (0.14±0.04)h,k a was (0.29±0.13),t 1/2α was (1.73±0.18)h,t 1/2β was (6.17±0.32)h,AUC was (693.80±23.50)μg·h·L -1. The absolute bioavailability was (31.95±3.4)%.The absorbtion of HCPT tablets was first-order kinetics; the lag time was short(0.14 h). The blood concentration of HCPT after administered orally, maintain high concentration at 6 h, and is high than 10 μg·L -1 at 12 h. Conclusion The absolute bioavailability of HCPT tablets was higher. The parameter of t 1/2 in oral administration was lagged longer than in injection administration, and maintain efficacy concentration for 12 hours. It showed that HCPT in body may exist intestine-hepatic circulation.

关 键 词：羟基喜树碱片剂 羟基喜树碱注射剂 药代动力学 绝对生物利用度 高效液相-荧光色谱 

分 类 号：R969.1[医药卫生—药理学] R979.1[医药卫生—药学]