Department of Anesthesiology, Ohio State University, Columbus, OH 43210, USA.
Reg Anesth Pain Med. 2012 Mar-Apr;37(2):145-51. doi: 10.1097/AAP.0b013e31823d0a80.
Bupivacaine extended-release liposome injection is an investigational local analgesic intended for use in postsurgical pain management. In recognition of the incompletely characterized association of bupivacaine use and cardiac effects, this article reviews the cardiac safety profile of this novel formulation of bupivacaine.
Findings from paired electrocardiograms (ECGs), corresponding pharmacokinetic assessments, and cardiovascular adverse events (AEs) in a phase 2, randomized, double-blind, dose-ranging study of bupivacaine extended-release (150, 300, 450, or 600 mg) or bupivacaine HCl 150 mg with epinephrine administered intraoperatively via wound infiltration in patients undergoing total knee arthroplasty (n = 138), were assessed for potential causality. Results from 4 phase 1 bupivacaine extended-release studies that also obtained ECG and/or Holter monitor findings (n = 169) were assessed. In addition, incidences of cardiovascular AEs reported across 10 bupivacaine extended-release wound infiltration studies (n = 1459) were pooled and assessed.
In the phase 2 study, mean change from baseline in QRS duration and QTcF duration across dose levels of bupivacaine extended-release was similar (range, -1 to +4 milliseconds and -7 to -10 milliseconds) compared with bupivacaine HCl (-1 millisecond and -6 milliseconds). Mean change from baseline in heart rate, PR interval, and QRS interval was similar between treatment groups as well. No clinically relevant ECG changes or cardiac AEs with bupivacaine extended-release were observed in the other clinical studies.
A focused assessment of ECG data from a phase 2 study and cardiac findings/AEs data from other studies in the bupivacaine extended-release development program did not reveal any cardiac safety issues.
布比卡因脂质体注射液是一种正在研究中的局部镇痛剂，旨在用于术后疼痛管理。鉴于布比卡因使用与心脏效应之间的关联不完全明确，本文综述了这种新型布比卡因制剂的心脏安全性概况。
在一项 2 期、随机、双盲、剂量范围研究中，对接受全膝关节置换术的患者（n=138）进行了配对心电图（ECG）、相应的药代动力学评估以及布比卡因延长释放（150、300、450 或 600mg）或布比卡因 HCl 150mg 联合肾上腺素术中通过伤口浸润给药的心脏安全性评估，评估了潜在的因果关系。还评估了 4 项布比卡因延长释放 1 期研究的 ECG 和/或动态心电图监测结果（n=169）。此外，还汇总并评估了 10 项布比卡因延长释放伤口浸润研究（n=1459）中报告的心血管不良事件发生率。
在 2 期研究中，与布比卡因 HCl 相比（-1 毫秒和-6 毫秒），布比卡因延长释放各剂量水平的 QRS 持续时间和 QTcF 持续时间的平均基线变化相似（范围：-1 至+4 毫秒和-7 至-10 毫秒）。治疗组之间的心率、PR 间隔和 QRS 间隔的平均基线变化也相似。在其他临床研究中，未观察到布比卡因延长释放的任何临床相关心电图变化或心脏不良事件。
对 2 期研究的 ECG 数据进行集中评估以及布比卡因延长释放开发项目中的其他研究的心脏发现/不良事件数据并未显示出任何心脏安全性问题。
