重组人血管内皮抑制素的人体药动学  

Pharmacokinetics of recombinant human endostatin in healthy volunteers and patients with advanced solid tumors

作　　者：朱仲玲 薛津怀[1] 王听说[1] 阎昭[1] 

机构地区：[1]天津医科大学附属肿瘤医院临床药理研究室,天津300060

出　　处：《中国新药与临床杂志》2007年第11期809-812,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的:评价重组人血管内皮抑制素(rh-endostatin)注射液在健康受试者和肿瘤病人体内的药动学特征。方法:24名健康受试者随机分为3组,单次静脉滴注rh-endostatin剂量分别为60、120和180 mg·m^(-2)。10名恶性肿瘤病人,每日给药剂量10mg·m^(-2),连续7 d。用酶联免疫试剂盒(ELISA)测定人血浆中rh-endostatin浓度。采用DAS 2.0药动学软件进行药动学参数的分析和计算。结果:单次静脉滴注不同剂量rh-endostatin后,c_(max)分别为(4.9±s 1.3)、(6.5±2.0)和(8±4)mg·L^(-1);AUC_(0～72)分别为(18±5)、(28±10)和(36±10)mg·h·L^(-1);t_(1/2β)分别为(8±19)、(6±9)和(27±27)h。Rh-endostatin连续给药7 d,c_(min)^(ss)为(0.86±0.16)mg·L^(-1),c_(min)^(ss)为(0.17±0.05)mg·L^(-1),c_(av)^(ss)为(0.27±0.09)mg·L^(-1),AUC^(ss)为(6.5±2.2)mg·h·L^(-1)。结论:国产rh-endostatin注射液在人体内表现为线性药动学特征,药时曲线符合二室模型,连续给药未发现药物在体内蓄积。AIM： To evaluate the pharmacokinetics of recombinant human endostatin （rh-endostatin） in 24 healthy volunteers and 10 patients with advanced solid tumors. METHODS： Twenty-four healthy volunteers for single-dose pharmacokinetic study received rh-endostatin in 3 dosing cohorts. Eight volunteers each were given 60, 120 and 180 mg·m^-2, respectively. Rh-endostatin was administered to 10 patients for a multiple-dose pharmacokinetic study at a dose of 10 mg·m^-2 daily for a 7-day continuous intravenous infusion. Determination of the plasma concentration for all 34 individuals was performed by enzyme-linked immunosorbent assay （ELISA） . DAS 2.0 was applied to assess the plasma rh-endostatin concentration-time data. RESULTS： In the single-dose pharmacokinetic study, cmax were （4.9±s 1.3）, （6.5± 2.0） and （8± 4） mg·L^-1; AUC0-72were （18 ± 5）, （28 ± 10） and （36 ± 10） mg·h·L^-1; t1/2β were （8 ± 19）, （6± 9） and （27 ± 27） h. In the multiple-dose pharmacokinetic study, the main parameters were as follow： cmax^ss （0.86 ± 0.16） mg·L^-1, cmin^ss （0.17 ± 0.05） mg·L^-1, cav^ss （0.27 ± 0.09） mg·L^-1 and AUC^ss （6.5 ± 2.2） mg·h·L^-1. CONCLUSION： Rh-endostatin displays apparent linear pharmacokinetic behavior. The plasma concentration-time curve is fitted to two-compartment pharmacokinetic model. No accumulation was observed during the continuous administration.

关 键 词：血管生成 血管内皮抑制素 免疫酶技术 药动学 

分 类 号：R969.1[医药卫生—药理学]