Clinical Specialist, Critical Care and Cardiology, Memorial Hermann Memorial City Medical Center, 921 Gessner Road, Houston, TX 77024, USA.
Clin Drug Investig. 2013 Feb;33(2):109-15. doi: 10.1007/s40261-012-0043-z.
Local anaesthetics are often used as part of multimodal pain management techniques to manage postsurgical pain and lessen the need for opioid analgesics; however, the duration of action of traditional formulations of local anaesthetics is short. Liposome bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound. This article provides a summary of the pharmacokinetic profile of liposome bupivacaine compared with bupivacaine HCl based on data compiled from four randomized, active- and placebo-controlled trials that included pharmacokinetic assessments following single administrations of study drug. Each study evaluated the safety, efficacy and pharmacokinetic profile of liposome bupivacaine in separate surgical populations (patients undergoing inguinal hernia repair, total knee arthroplasty, haemorrhoidectomy or bunionectomy). Pharmacokinetic parameters included maximum plasma drug concentration (C(max)), area under the curve (AUC) for plasma bupivacaine concentration over time extrapolated to infinity (AUC(∞)), time to observed C(max) (t(max)) and terminal elimination half-life of bupivacaine (t(½)). The studies assessed single administrations of liposome bupivacaine at dose levels ranging from 106 to 532 mg or bupivacaine HCl 100 to 150 mg or placebo (0.9 % sodium chloride) given locally via wound infiltration at the end of surgery prior to wound closure. Male and non-pregnant female patients (n = 253) aged ≥18 years, scheduled to undergo surgery as per the specific protocol for each study, were enrolled. Patient characteristics were stratified by liposome bupivacaine doses ≤266 mg and >266 mg, and bupivacaine HCl treatment arms. Pharmacokinetic parameters for liposome bupivacaine doses of 106, 266, 399 and 532 mg were compared. Plasma concentration versus time profiles were quantitatively similar across these four dose levels of liposome bupivacaine, with an initial peak occurring within 1 h after administration followed by a second peak about 12-36 h later. The overall incidence of adverse events was lower in the liposome bupivacaine ≤266-mg group than the liposome bupivacaine >266-mg and bupivacaine HCl groups (100- or 150-mg doses). In summary, liposome bupivacaine was well tolerated across the four studies and varied surgical models, and exhibited bimodal kinetics with rapid uptake observed during the first few hours and prolonged release through 96 h after administration.
局部麻醉剂通常作为多模式疼痛管理技术的一部分，用于管理手术后疼痛并减少对阿片类镇痛药的需求；然而，传统局部麻醉剂制剂的作用持续时间较短。脂质体布比卡因是一种新型的多泡制剂，设计用于快速吸收，延长布比卡因的释放，并在单次术中给药至手术伤口后提供镇痛作用。本文根据四项随机、阳性和安慰剂对照试验中汇总的数据，比较了脂质体布比卡因与盐酸布比卡因的药代动力学特征，这些试验均在单次给予研究药物后进行了药代动力学评估。每项研究均评估了脂质体布比卡因在不同手术人群（接受腹股沟疝修补术、全膝关节置换术、痔切除术或拇囊炎切除术的患者）中的安全性、疗效和药代动力学特征。药代动力学参数包括最大血浆药物浓度（C(max)）、时间外推至无穷大的血浆布比卡因浓度的曲线下面积（AUC(∞)）、观察到的 C(max)（t(max)）和布比卡因的终末消除半衰期（t(½)）。这些研究评估了脂质体布比卡因在 106 至 532mg 剂量水平和盐酸布比卡因 100 至 150mg 剂量水平或安慰剂（0.9%氯化钠）的单次给药，这些药物在手术结束时通过伤口浸润局部给予，然后关闭伤口。纳入了年龄≥18 岁的男性和非妊娠女性患者（n=253），这些患者根据每项研究的具体方案计划接受手术。患者特征按脂质体布比卡因剂量≤266mg 和>266mg 以及盐酸布比卡因治疗臂进行分层。比较了脂质体布比卡因 106、266、399 和 532mg 剂量的药代动力学参数。脂质体布比卡因的四个剂量水平的血浆浓度-时间曲线相似，给药后 1 小时内出现初始峰值，然后约 12-36 小时后出现第二个峰值。脂质体布比卡因≤266mg 组的不良事件总发生率低于脂质体布比卡因>266mg 组和盐酸布比卡因组（100 或 150mg 剂量）。总之，脂质体布比卡因在四项研究和不同的手术模型中均具有良好的耐受性，表现出双模态动力学特征，在最初的几个小时内迅速吸收，并在给药后 96 小时内持续释放。
