Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.

IF 2.7 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI:10.1007/s40261-025-01419-w

Stevie Pope, Christopher Crean, Sarah Thrasher, Hanghang Xu, P J Chen, Lee Chen, DeeDee Hu, Erol Onel

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引用次数: 0

Abstract

Background and objective: There is a significant medical need for improved long-acting local anesthetics to decrease postsurgical pain and reduce postoperative opioid use. While ropivacaine is considered a safer local anesthetic than bupivacaine, no long-acting ropivacaine formulation is currently marketed. Available formulations of bupivacaine show inconsistent pharmacokinetics (PK) among different surgical models, and inconsistency in PK may lead to a reluctance to use the medication owing to fear of local anesthetic systemic toxicity (LAST) or unreliable efficacy. CPL-01 is a novel extended-release formulation of ropivacaine. This analysis used existing published literature to compare the PK of CPL-01 and liposomal bupivacaine (LB) across five surgical models.

Methods: Published results of LB PK were used to construct dose-normalized curves in total knee arthroscopy, hemorrhoidectomy, and bunionectomy after a 200 mg dose, which were compared with a 200 mg dose of CPL-01 in abdominoplasty, herniorrhaphy, and bunionectomy.

Results: The shape of the CPL-01 systemic concentration curves was consistent across multiple surgical models; however, in LB it was not. The median time to peak concentration (T_max) of CPL-01 was 8-12 h and the median T_max of LB varied from < 1 to 36 h. CPL-01 showed tighter ranges in average peak concentration (C_max) compared with average concentration (C_avg) ratios (less "swing") throughout 72 h, suggesting a more predictable and consistent release over time compared with the biphasic release in LB, with two distinct T_max peaks.

Conclusions: CPL-01 demonstrates a more predictable and consistent release of ropivacaine over time, in contrast to LB's erratic and biphasic release of bupivacaine. If approved, the predictability of CPL-01 PK may give physicians greater confidence in more consistent efficacy and less fear of inadvertent LAST.

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长效局部镇痛药的药代动力学比较：新型缓释罗哌卡因CPL-01与布比卡因脂质体暴露一致且可预测。

背景和目的：改进长效局麻药以减少术后疼痛和减少术后阿片类药物的使用具有重要的医学需求。虽然罗哌卡因被认为是一种比布比卡因更安全的局部麻醉剂，但目前还没有长效罗哌卡因制剂上市。现有的布比卡因配方在不同手术模式中显示出不一致的药代动力学（PK），而PK的不一致可能导致由于担心局部麻醉全身毒性（LAST）或不可靠的疗效而不愿使用该药物。CPL-01是一种新型罗哌卡因缓释制剂。本分析使用现有已发表的文献比较了5种手术模型中CPL-01和布比卡因脂质体（LB）的PK。方法：利用已发表的LB - PK结果构建200 mg剂量后全膝关节镜、痔疮切除术和拇囊炎切除术的剂量归一化曲线，并与200 mg剂量的CPL-01在腹部成形术、疝修补术和拇囊炎切除术中进行比较。结果：不同手术模型的CPL-01全身浓度曲线形状一致；然而，在LB中并非如此。CPL-01的中位峰浓度（Tmax）时间为8 ~ 12 h， LB的中位峰浓度（Tmax）变化范围为< 1 ~ 36 h。与平均浓度（Cavg）比相比，CPL-01在72 h内的平均峰浓度（Cmax）范围更窄（“摆动”更小），表明与LB的双相释放相比，CPL-01的释放随时间更可预测和一致，有两个不同的Tmax峰。结论：与LB的不稳定和双相布比卡因释放相比，CPL-01表现出更可预测和一致的罗哌卡因释放。如果获得批准，CPL-01 PK的可预测性可能会让医生对更一致的疗效有更大的信心，并减少对意外死亡的恐惧。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.