重组人胰高血糖素样多肽-1(7-36)在健康人体的药代动力学  

Pharmacokinetics of recombined human glucagonlike peptide-1(7-36) in Chinese healthy volonteers

作　　者：方翼[1] 柴栋[1] 郑专杰[1] 王锡萍[1] 王睿[1] 

机构地区：[1]解放军总医院临床药理室,北京100853

出　　处：《中国临床药理学杂志》2006年第4期250-253,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究重组人胰高血糖素类多肽-1（7-36）[rhGLP-1（7-36）]（促胰岛素生成药）在健康志愿者的药代动力学.方法选择12,9名健康志愿者,分别单次（0.1,0.15,0.2 mg）和多次（0.2 mg）皮下注射rhGLP-1（7-36）,连续5日,用荧光酶联免疫分析法测定其血药浓度,用DAS软件计算其药代动力学参数.结果单次：药-时曲线符合一房室模型,Cmax、AUC0-t随剂量增加而增加,tmax约为19～21 min,ti/2为10～14min.多次：首次与末次给药后的Cmax分别为（726.76±94.07）,（737.15±72.12）ng·L-1;tmax为18min左右;t1/2为15～17 min.结论在0.1～0.2 mg内,过程呈一级线性动力学特征,体内无蓄积,耐受性较好.Objective To investigate the pharmacokinetics of recombined human glucagon - like peptide - 1 （7 -：36） [ rhGLP - 1 （7 - 36） ] after subcutaneous injection in single dose and muhidose in Chinese healthy volunteers. Methods The drug concentration of plasma sample from 12 volunteers after single dose subcutaneous injection 0. 1,0. 15, 0. 2 mg rhGLP - 1 （ 7 - 36 ） was determined by enzyme linked immunosorbent assay（ELISA） method. The drug concentration of plasma sample from 9 volunteers after muhidose subcutaneous injection 0. 2mg 5min before meal 3 times per day and 5 days total was determined by ELISA method. The pharmacokinetic parameters were calculated by DAS software. Results The plasma concentration time curve fits one compartment model after single time subcutaneous injection rhGLP - 1 （7 - 36） 0. 1, 0. 15,0.2 mg. The Cmax AUC0-1 increased along with the dose. The tmax was 19 - 21min approximately; t1/2 was 10 - 14 min. The main pharmacokinetic parameters of the first time and the last time of the fifth day after muti - dose subcutaneous rhGLP - 1 （ 7 - 36 ） Cmax was （ 726.76 ± 94.07）,（737.15±72.12） ng· L^-1; tmax was （18.33 ±2.50） min; t1/2 was 15 - 17 min. Conclusion The pharmacokinetics of the drug in the dosage range of 0. 1 - 0. 2 mg in human body nearly fit one grade linear dynamic feature. The pharmacokinetic parameters of drug subcutaneous injection 5 min before meal 3 times 5 day were not changed with no accumulation nor sevare ad -dictive effect.

关 键 词：重组人胰高血糖素类多肽-1(7-36)冻干粉 药代动力学 荧光酶联免疫分析法 

分 类 号：R711.31[医药卫生—妇产科学] R984[医药卫生—临床医学]