9-硝基喜树碱胶囊在肿瘤病人体内的药动学  

Pharmacokinetics of 9-nitrocamptothecin capsule in patients with advanced solid tumors

作　　者：朱仲玲 阎昭[1] 王华庆[1] 薛津怀[1] 杨华[1] 郝希山[1] 

机构地区：[1]天津医科大学附属肿瘤医院、天津市“肿瘤防治”重点实验室,天津300060

出　　处：《中国新药与临床杂志》2009年第5期346-350,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家高技术研究发展计划863课题(2004AA2Z3720)

摘　　要：目的评价单次和连续口服9-硝基喜树碱胶囊在肿瘤病人体内的药动学特征。方法恶性肿瘤病人随机分为:单次给药(n=22)分3组,给药剂量分别为1.25、1.5和1.75mg·m-2;连续给药(n=13)分3组,每日给药剂量分别为1.25、1.5和1.75mg·m-2,连续服用4d。HPLC-UV法测定人血浆中9-硝基喜树碱的浓度,采用DAS2.0药动学软件分析和计算药动学参数。结果单次给药3个剂量组ρmax分别为(76±s49)、(81±30)和(98±36)μg·L-1,AUC0～24h分别为(0.5±0.3)、(0.8±0.5)和(0.9±0.4)mg·h·L-1;连续给药3个剂量组ρssav分别为(75±108)、(43±28)和(56±46)μg·L-1,AUCss分别为(1.8±2.6)、(1.0±0.7)及(1.3±1.1)mg·h·L-1。体内未见药物蓄积。结论在1.25～1.75mg·m-2剂量范围内,9-硝基喜树碱的ρmax和AUC0～24h随着给药剂量的增加而增加。AIM To study the pharmaeokinetics of 9-nitrocamptothecin （9-NC） capsule in patients with advanced solid tumors. METHODS Twenty-two patients in single-dose group were divided into 3 dose cohorts and received 9-NC capsule 1.25, and 1.75 mg·m^-2, respectively. Thirteen patients in multiple-dose group were divided into 3 dose cohorts and received respectively 9-NC capsule 1.25, 1.5 and 1.75 mg ·m^-2 for 4 consecutive days. The concentration of 9-NC in plasma was determined by high performance liquid chromatography-ultraviolet method. DAS2.0 was applied to assess the plasma concentration-time data of 9-NC.RESULTS In single-dose group, pmax were （76 ± s 49）, （81 ± 30） and （98 ± 36）μg·L^-1; AUC0-24h were （0.5 ± 0.3）, （0.8±0.5） and （0.9 ± 0.4） mg·h·L^-1. Pav^ss were （75 ± 108）, （43 ± 28） and （56 ± 46） μg·L^-1; and AUC^ss were （1.8 ± 2.6）, （1.0 ± 0.7） and （1.3 ± 1.1） mg·h·L^-1, respectively. No aecumulation wasobserved. CONCLUSION The plasma concentration and AUC0-24h of 9-NC increased with the dosage ranging from 1.25 to 1.75 mg·m^-2.

关 键 词：喜树碱 药动学 色谱法 高压液相 肿瘤 9-硝基喜树碱 

分 类 号：R969[医药卫生—药理学]