Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia.
The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers.
Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2–5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities.
Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography.
The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals.
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Editorial and medical writing assistance was provided by Michael D. Morren, RPh, MBA, of Peloton Advantage, LLC, supported by Pacira Pharmaceuticals, Inc., the manufacturer of liposomal bupivacaine. The authors were fully responsible for the content, editorial decisions, and opinions expressed in the current article. The authors did not receive an honorarium related to the development of this manuscript.
Conflicts of interest
D. Rice was a consultant for Pacira Pharmaceuticals, Inc. J. W. Heil has no conflicts of interest to disclose. L. Biernat is employed by Medpace Clinical Pharmacology Unit, the institution contracted to conduct the study, supported by Pacira Pharmaceuticals, Inc.
Source of funding
This study was funded by Pacira Pharmaceuticals, Inc.
Ethical approval/informed consent
The study was approved by an independent ethics committee (Western Institutional Review Board, Puyallup, WA, USA), and all participants provided written informed consent before any study procedures were performed. The study was conducted from August to September 2014 in accordance with guidelines established by the International Council for Harmonisation for Good Clinical Practice  and the Declaration of Helsinki.
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Rice, D., Heil, J.W. & Biernat, L. Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers. Clin Drug Investig 37, 249–257 (2017). https://doi.org/10.1007/s40261-017-0495-2
- Inguinal Hernia Repair
- Repeated Dose
- Central Nervous System Toxicity
- Wound Infiltration