FDA-Approved NOCITA® (bupivacaine liposome injectable solution)
Bupivacaine is an aminoamide local anesthetic. The chemical structure and nomenclature for bupivacaine is shown in Figure 4. The empirical formula for bupivacaine is C28H26N2O, and the molecular weight is 288.43 Daltons.21
Mechanism of Action
Bupivacaine provides local analgesia by reversibly deactivating sodium channels on neuronal cell membranes, preventing the generation and propagation of nerve impulses. Because it is a weak base (pKa = 8), bupivacaine is present in only small concentrations as uncharged molecules at tissue pH. This un-ionized form provides a lipophilicity that permits the drug to traverse the cell membrane. Upon entering the cell, bupivacaine binds to the intracellular portion of voltage-gated sodium channels and blocks sodium influx into nerve cells, preventing depolarization. Without depolarization, no initiation or conduction of a pain signal can occur. Small nociceptive fibers, specifically unmyelinated C fibers and myelinated Aδ fibers, are blocked before larger sensory Aβ and motor Aα fibers.22
To provide a longer duration of anesthesia than bupivacaine HCl or other local anesthetics, NOCITA is in an encapsulated liposomal formulation. The multivesicular liposome particles in NOCITA are made up of a honeycomb-like structure consisting of many nonconcentric compartments that contain bupivacaine for gradual, local release (Figure 5). In vivo, NOCITA releases drug over an extended period by erosion of the exterior surface and reorganization of the particles’ lipid membranes.23
21. NOCITA® [package insert]. Leawood, KS: Aratana Therapeutics, Inc.; 2016.
22. Covino BG. Pharmacology of local anesthetic agents. Br J Anaesth. 1986;58(7):701-716.
23. Chahar P, Cummings KC. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012;5(257):264.