PROLONGED ANALGESIA WITH LIPOSOMAL BUPIVACAINE IN A MOUSE MODEL

Background and Objectives. Currently available local anesthetics have relatively limited duration of action and some may cause severe system ic toxicity. An ultralong lasting local anesthetic would be useful to produce prolonged intraoperative anesthesia and extended postoperative analgesia. The goal of this study was to synthesize a sustained relea se local anesthetic formulation that would produce prolonged sensory b lock and decrease the possibility of systemic toxicity. Methods. The e ffect of liposomes containing 1.1% bupivacaine on duration of sensory block of the mouse tail was compared with equivalent concentrations of bupivacaine with and without epinephrine. Analgesia was assessed usin g the tail flick test. Systemic toxicity (LD50) was assessed after int raperitoneal injection and in vitro release rates were compared by dia lysis technique for liposomal and plain bupivacaine. Results. Sensory block was significantly prolonged with liposomal bupivacaine (130 +/- 38 minutes) compared to plain bupivacaine (46 +/- 11 minutes, P < .01) or bupivacaine with epinephrine (81 +/- 28 minutes, P < .05). The LD5 0 was significantly lower for plain bupivacaine (61 mg/kg, 95% confide nce intervals 47-79) than for liposomal bupivacaine (291 mg/kg, 95% co nfidence intervals 201-422). The time to 50% in vitro release through a dialysis membrane for liposomal bupivacaine (28 +/- 9 minutes) was m arkedly prolonged compared to plain bupivacaine (7 +/- 1 minutes). Con clusions. This study shows that liposomal encapsulation of bupivacaine significantly prolongs duration of action and greatly decreases syste mic toxicity of the drug. These findings may be promising for the futu re production of formulations of ultralong lasting local anesthetics w ith enhanced efficacy and safety.