Bupivacaine Extended-Release Liposome Injection Exhibits a Favorable Cardiac Safety Profile
Bupivacaine Extended-Release Liposome Injection Exhibits a Favorable Cardiac Safety Profile
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DOI：
10.1097/aap.0b013e31823d0a80
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发表时间：
2012-03-01
影响因子：
5.1
通讯作者：
Morganroth, Joel
中科院分区：
文献类型：
--
作者：
Bergese, Sergio D.;Onel, Erol;Morganroth, Joel
背景和目的：布比卡因缓释脂质体注射液是一种正在研究的局部镇痛药，旨在用于术后疼痛管理。鉴于布比卡因使用与心脏影响之间的关系尚未完全确定，本文综述了布比卡因这种新型制剂的心脏安全性概况。方法：布比卡因 2 期、随机、双盲、剂量范围研究中的配对心电图 (ECG)、相应的药代动力学评估和心血管不良事件 (AE) 的结果 缓释剂（150、300、450 或 600 mg）或盐酸布比卡因 150 mg 联合肾上腺素，在接受全膝关节置换术的患者术中通过伤口浸润给药（n = 138），评估其潜在因果关系。 4 项 1 期布比卡因缓释研究的结果，还获得了心电图和/或动态心电图监测结果（n = 169）进行了评估。此外，还对 10 项布比卡因缓释伤口浸润研究 (n = 1459) 报告的心血管 AE 发生率进行了汇总和评估。结果：在第 2 期研究中，与盐酸布比卡因（-1 毫秒和 -6 毫秒）相比，布比卡因缓释剂量水平下 QRS 时限和 QTcF 时限相对于基线的平均变化相似（范围为 -1 至 +4 毫秒和 -7 至 -10 毫秒）。治疗组之间心率、PR 间期和 QRS 间期相对于基线的平均变化也相似。在其他临床研究中，没有观察到与布比卡因缓释剂相关的临床相关心电图变化或心脏 AE。 结论：对 2 期研究的心电图数据和布比卡因缓释剂开发计划中其他研究的心脏结果/AE 数据进行集中评估，没有发现任何心脏安全问题。 (Reg Anesth Pain Med 2012；37:145-151)
Background and Objectives: 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.Methods: 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. Results: 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.Conclusions: 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. (Reg Anesth Pain Med 2012;37:145-151)