High-Dose Bupivacaine Remotely Loaded into Multivesicular Liposomes Demonstrates Slow Drug Release Without Systemic Toxic Plasma Concentrations After Subcutaneous Administration in Humans

Peak plasma bupivacaine concentrations were not different in the 2 groups, despite a 4-fold increase in total bupivacaine dose administered in the novel liposomal preparation. The delayed elimination and prolonged redistribution of liposomal bupivacaine to plasma is compatible with the depot-related slow-release effect leading to the prolonged pharmacodynamic effect previously reported.