Time to Analgesia Onset and Pharmacokinetics After Separate and Combined Administration of Liposome Bupivacaine and Bupivacaine HCl: Considerations for Clinicians

Jeffrey Gadsden1, *, William J. Long2
1 Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA
2 Insall Scott Kelly Institute for Orthopaedics and Sports Medicines, New York, NY, USA

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Creative Commons License
© Gadsden and Long; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Anesthesiology, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27705-4699 USA; Tel: 919-681-6437; Fax: 919-684-8994; E-mail:



Liposome bupivacaine is a prolonged-release bupivacaine formulation indicated for single-dose administration into the surgical site to produce postsurgical analgesia.


An overview of time to onset of analgesia observed with liposome bupivacaine in human studies is provided, as well as a summary of data from pharmacokinetic studies including those that assessed pharmacokinetics after separate versus coadministration of liposome bupivacaine and bupivacaine HCl.


Data from multiple studies show that local administration of liposome bupivacaine is associated with rapid onset and effective analgesia after surgery. However, the efficacy profile observed in controlled settings may not replicate the profile observed in clinical practice; time to onset may be impacted by nonpharmacologic factors, such as amount of drug given, location and relative vascularity, and variances in surgical techniques. Some clinicians coadminister or admix bupivacaine HCl and liposome bupivacaine based on the supposition that adjuvant use will result in more rapid onset of efficacy. To date, no clinical studies have been conducted comparing pain-related outcomes following coadministration versus liposome bupivacaine alone. Preclinical pharmacokinetic studies have assessed the potential impact of combined use, which resulted in predictable, additive systemic exposure without compromising the prolonged-release profile of liposome bupivacaine, and without signs of toxicity.


Based on available data and approved package insert, in the setting of wound infiltration, clinicians have the flexibility to administer liposome bupivacaine alone, coadminister separately with bupivacaine HCl, or admix with bupivacaine HCl prior to injection, providing the bupivacaine HCl dose does not exceed 50% of the liposome bupivacaine dose.

Keywords: Analgesia postsurgical, Bupivacaine HCl, Clinical efficacy, Infiltration, Liposome bupivacaine, Pharmacokinetics.