【罂粟摘要】普瑞巴林治疗剂量对清醒家兔的QTc间隔影响
普瑞巴林治疗剂量对清醒家兔的QTc间隔影响
贵州医科大学 麻醉与心脏电生理课题组
翻译：刘云琴 编辑：佟睿 审校：曹莹
普瑞巴林（PRG）是一种新的抗癫痫药物，已被用于部分性癫痫患者的辅助治疗。尽管已知许多神经精神药物和非心脏药物可以延长心室复极，如QTc间期延长可引起尖端扭转型室性心动过速，但关于给予PRG后清醒实验动物QT间期特征的可用数据有限。本研究在规定的时间间隔内评估了不同治疗剂量口服PRG对家兔心率（HR）、QT和QTc值的影响。
这项研究涉及28只新西兰兔子，雌雄不限，年龄在8到12个月之间。动物被分成四个组。对照组给予生理盐水0.5ml/只。第一组、第二组和第三组分别以1.25mg/kg、2.5mg/kg和5mg/kg单剂量口服PRG。记录采集实验前及实验第1、2、4和6小时的心电图。根据心电图记录确定心率、QT和qtc值。
与基线值相比，所有组的心率均增加。与对照组相比，第二组在第4小时（p<0.001）、第三组在第2小时（p<0.05）和第4小时（p<0.001）的QTc间期增加明显。应用PRG后，QTc在第1小时开始延长至第4小时，然后在第6小时变为基线值。第二组和第三组在用药后第2小时获得的QTC值（p<0.05）和第二组在第4小时时获得的QTC值（p<0.001）与CG显著不同。PRG治疗组的心率、QT和QTc值的变化具有时间和剂量依赖性（p<0.001）。
Alp R,Citil M,Uzun M, et al. Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits[J]. European Review for Medical and Pharmacological Sciences, 2008, 12(4):223.
Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits
Abstract
Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive therapy for partial seizures in patients. Although many neuro-psychiatric and non-cardiac drugs are known to prolong ventricular repolarization as manifested by QTc prolongation on ECG of which provokes torsades de pointes, there is limited data available regarding the characteristics of QT interval in conscious laboratory animals after PRG administration. For that purpose, effects of different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and QTc values in rabbits were evaluated at a predefined time interval in this research.
The study involved 28 New Zealand rabbits of both sexes, aged between 8 and 12 months. Animals were divided into four equal groups. Rabbits in control group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, respectively. ECG records were taken before experiment (baseline) and at 1st, 2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph. HR, QT and QTc values were determined from ECG records.
Heart rates increased in all groups when compared to baseline values. The increases were evident at 4th h in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III compared with CG. After application of PRG, QTc began to prolong at 1st h through the 4th of experiment and then turned to baseline values at 6th h of the experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and 4th h (p< 0.001) of application in group III were significantly different from CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time and dose dependent (p < 0.001).
Increase in HR and QTc prolongation determined in PRG given rabbits may implied that clinicians should take care of these changes when using this drug and further studies are required to fully understand the mechanism involved.