伊布利特注射液的中国人人体药动学  

Pharmacokinetic study of ibutilide injection in Chinese healthy volunteers

作　　者：田蕾[1] 蒋娟娟[1] 黄一玲[1] 华潞[1] 况扶华[1] 李一石[1] 

机构地区：[1]中国医学科学院阜外心血管病医院临床药理中心卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国新药与临床杂志》2006年第7期531-534,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：863国家攻关项目<临床试验关键技术及平台研究>(2002AA22341A;2004AA2Z3760)

摘　　要：目的：评价健康中国人单次静脉注射伊布利特后的药动学特征。方法：40例健康男性受试者随机分为6组,分别静脉注射伊布利特0．005 mg·kg^(-1)(n=4),0．01 mg·kg^(-1)(n=10),0．02 mg·kg^(-1)(n=6),0．5 mg (n=6),0．75 mg(n=6)和1．0 mg(n=8)。采用液相色谱-质谱联用法测定血浆伊布利特浓度。结果：给药后各剂量组的c_(max)和AUC随给药剂量的增加而成比例增加,c_(max)为(1．9±s0．6)～(7．2±1．9)μg·L^(-1),AUC_(0～24)为(69±21)～(236±63)μg·min·L^(-1),线性相关显著(P＜0．01)。伊布利特的t_(1/2)为8 h左右(4～11 h),V_d为(47±12)～(63±18)L·kg^(-1),CJ为(68±20)～(85±26)mL·min^(-1)·kg^(-1),在各剂量组之间没有显著差别(P＞0．05)。结论：在本研究剂量范围内,静脉注射伊布利特耐受性良好,其体内处置过程符合线性动力学特征而无饱和性。AIM： To investigate the pharmacokinetic profiles of ibutilide intravenous administration on Chinese male healthy volunteers with ascending doses after single application. METHODS： Forty male volunteers aged from 18 to 35 a were randomized to receive 10-minute infusion of ibutilide with 0.005 mg·kg^-1, 0.01 mg·kg^-1, 0.02 mg· kg＆-1, 0.5 mg, 0.75 mg, or 1.0 mg, respectively. The plasma concentrations of ibutilide were determined by a validated LC/MS/MS method. RESULTS： In all the six dose groups, cmax and A UC increased in a dosedependent manner, cmax ranged from （1.9 ± 0.6） to （7.2 ± 1.9）μg·L^-1, and AUC0-24 ranged from （69 ± 21） to （236 ±63 ）μg·min·L^-1, with significant linear correlation（P 〈 0.01 ）. The elimination half-life of ibutilide was about 8 h （4 - 11 h）, and there was no significant difference in t1/2, Vd, and Cl among the six different dosing groups （P 〉0.05）. CONCLUSION： Intravenous injection of ibutilide is well tolerated within the assigned concentrations of this study coinciding with linear pharmacokinetic characteristics without saturation tendency.

关 键 词：伊布利特 药动学 色谱法 高压液相 光谱法 质量 电喷雾电离 

分 类 号：R972.6[医药卫生—药品] R969.1[医药卫生—药学]