摘要
目的静脉注射伊布利特(抗心律失常药物)对健康人及房颤与房扑患者用药后心电图QTc间期变化的比较研究。方法 40例健康男性随机分为6组(每组分别为4,10,6,6,6,8人),分别静脉注射伊布利特5,10,20μg.kg-1及单次给药0.5,0.75,1.0mg。房颤、房扑患者各100例应用伊布利特(1mgiv;体质量小于60kg者,按0.01mg·kg-1)转复心律治疗,必要时重复给药1次。结果健康受试者药后QTc间期明显延长,峰值出现于给药完成后。5,10,20μg.kg-1组RQTc均值最大值分别为(469±7),(592±35)及(678±14)ms;0.5,0.75,1.0mg组的最大值分别为(605±39),(616±8)及(683±9)ms。100例房颤、房扑患者的药后QTc间期延长,峰值出现于静脉注射结束即刻;1次给药者QTc峰值为(476±9)ms;2次给药者QTc峰值为(510±8)ms,于4h恢复基线水平。相同给药方式,健康受试者较患者的QTc间期延长更为显著(P<0.05)。有43%接受2次给药的患者,QTc可延长至500～600ms;9%可延长至600ms以上。发生1例尖端扭转型室性心动过速(1%)、2例室性心动过速(2%)。结论静脉注射伊布利特后,中国健康受试者和房颤、房扑患者QTc间期均明显延长,最大可达600ms以上;但健康人QTc延长较房颤、房扑患者更显著。要严密监测QTc间期至少应到药后4h。
Objective Ibutilide is widely used to convert atrial fibrilla- tion and artial flutter in clinical therapy, but there is no report on its effects on changes of QTe after administration. Methods Series QTc changes in Chinese population were investigated. In the open -label, increasing dose study, 40 health subjects were randomized in six groups with ibutilide 5, 10, 20 μg · kg^-1; 0.5, 0.75 or 1 mg. Then in the randomized, controlled study of atrial fibrillation and artial flutter patients, all subjects with QTc≤500 ms received ibutilide （1 mg iv, n = 100） over 10 minutes and a second infusion 10 minutes later as needed when QTc ≤600 ms. Results In Chinese health subjects, QTc prolongation reached their maximum of （469 ±7）ms, （592 ±35）ms and （678 ±14 ）ms for dose of 5, 10, 20 μg · kg^-1, and （605 ±39）, （ 616 ± 8） and （683 ± 9） ms for dose of 0. 5, 0. 75 and 1 mg respectively. QTc increased from （439 ±8） to （476 ±9） ms （15%） and from （476±9） to （510 ±8） ms （3.4%） immediately after first infusion and second infusion respectively （P 〈 0. 05 ） in atrial fibrillation and artial flutterpatients. QTc reached the peak rapidly around completion of ibutilide and increased 44% and 64% with doses of 0.01 mg · kg^-1 or 1 mg, which is much higher than what seen in AF or AFL patients with an increase of 13% in the present study （ P 〈 0.05 ）. Ibutilide increased QTe more than 600 ms also in patients with atrial fibrillation or artial flutter patients. Immediately after second infusion in patients ,43% and 9% patients had QTe 500 -600 ms and 〉 600 ms respectively. One torsade de pointes（TdP） developed and was converted by direct current electrical conversion. QTc peak occurred at the end of infusion, and returned to the baseline in 4 hours whatever in health subjects or in atrial fibrillation and artial flutter patients. Conclusion It suggests that the QTc value as inclusion criterion and as termination of ibutilide infusion threshold need fur
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2010年第7期488-494,共7页
The Chinese Journal of Clinical Pharmacology
