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Clinical Drug Investigation

Open Access 29-01-2025 | Pharmacokinetics | Brief Communication

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

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

Published in: Clinical Drug Investigation

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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 (Tmax) of CPL-01 was 8–12 h and the median Tmax of LB varied from < 1 to 36 h. CPL-01 showed tighter ranges in average peak concentration (Cmax) compared with average concentration (Cavg) 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 Tmax 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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Metadata
Title
Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine
Authors
Stevie Pope
Christopher Crean
Sarah Thrasher
Hanghang Xu
P. J. Chen
Lee Chen
DeeDee Hu
Erol Onel
Publication date
29-01-2025
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-025-01419-w