Liposomal local anesthetics

A 70-year-old male is currently in the operating room undergoing a total knee replacement. Just prior to placement of the implants, the surgeon asks about the role of liposomal bupivacaine to mitigate postoperative pain. Objectives 1. Describe the mechanism of action and pharmacokinetics of liposomal bupivacaine. 2. Discuss the efficacy of the medication versus placebo and other local anesthetics. 3. Analyze the safety profile of liposomal bupivacaine. 4. Elaborate on the use in orthopedic patients. 5. Review the use of this medication for peripheral nerve block. 1. Describe the mechanism of action and pharmacokinetics of liposomal bupivacaine Currently only one formulation of liposomal bupivacaine is FDA approved for use in humans. It is marketed under the brand name of Exparel. This formulation utilizes the same delivery system as another Pacira Pharmaceuticals product, DepoDur, liposomal morphine sulfate. At this time another liposomal product, SABER-bupivacaine, has been submitted to the FDA for possible approval but data on this product are not available in the literature. In the simplest terms, liposomes are microscopic spheres composed of an aqueous inner core surrounded by a phospholipid bilayer. This core can be loaded with various drugs, such as chemotherapeutics, antibiotics, or local anesthetics. They are biodegradable and non-immunogenic, making them an ideal delivery system for extended release. Further, the phospholipid bilayer has no inherent pharmacological activity. These liposomal preparations can be customized to be in various forms, from small unilamellar vesicles to large multilamellar vesicles (concentric cores) to multivesicular liposomes. The aqueous core pH can be adjusted to optimize bupivacaine uptake during manufacturing and to provide a predictable sustained-release system. Liposomal bupivacaine is a formulation utilizing the multivesicular concept (Figure 5.1) to allow for an extended delivery of a predictable amount of local anesthetic in the infiltrated site. This formulary is composed of a preservative-free aqueous suspension of multivesicular liposomes containing bupivacaine at a concentration of 13.3 mg/ml in a 20 ml vial, for a total of 266 mg of bupivacaine. While most of the bupivacaine is encapsulated, 3% of the total volume is present as free bupivacaine (affecting the pharmacokinetics as discussed below).