Grant G J, Vermeulen K, Langerman L, Zakowski M, Turndorf H
Department of Anesthesiology, New York University Medical Center, New York 10016.
Reg Anesth. 1994 Jul-Aug;19(4):264-9.
Currently available local anesthetics have relatively limited duration of action and some may cause severe systemic 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 release local anesthetic formulation that would produce prolonged sensory block and decrease the possibility of systemic toxicity.
The effect 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 using the tail flick test. Systemic toxicity (LD50) was assessed after intraperitoneal injection and in vitro release rates were compared by dialysis technique for liposomal and plain bupivacaine.
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 LD50 was significantly lower for plain bupivacaine (61 mg/kg, 95% confidence intervals 47-79) than for liposomal bupivacaine (291 mg/kg, 95% confidence intervals 201-422). The time to 50% in vitro release through a dialysis membrane for liposomal bupivacaine (28 +/- 9 minutes) was markedly prolonged compared to plain bupivacaine (7 +/- 1 minutes).
This study shows that liposomal encapsulation of bupivacaine significantly prolongs duration of action and greatly decreases systemic toxicity of the drug. These findings may be promising for the future production of formulations of ultralong lasting local anesthetics with enhanced efficacy and safety.
目前可用的局部麻醉药作用持续时间相对有限，且有些可能会引起严重的全身毒性。一种超长效局部麻醉药对于延长术中麻醉时间和术后镇痛时间将很有用。本研究的目的是合成一种缓释局部麻醉药制剂，该制剂可产生延长的感觉阻滞并降低全身毒性的可能性。
将含有1.1%布比卡因的脂质体对小鼠尾巴感觉阻滞持续时间的影响与同等浓度的含和不含肾上腺素的布比卡因进行比较。使用甩尾试验评估镇痛效果。通过腹腔注射评估全身毒性（半数致死量），并通过透析技术比较脂质体布比卡因和普通布比卡因的体外释放率。
与普通布比卡因（46±11分钟，P<.01）或含肾上腺素的布比卡因（81±28分钟，P<.05）相比，脂质体布比卡因的感觉阻滞时间显著延长（130±38分钟）。普通布比卡因的半数致死量（61mg/kg，95%置信区间47-79）显著低于脂质体布比卡因（291mg/kg，95%置信区间201-422）。与普通布比卡因（7±1分钟）相比，脂质体布比卡因通过透析膜的体外释放50%的时间显著延长（28±9分钟）。
本研究表明，布比卡因的脂质体包封显著延长了作用持续时间，并大大降低了该药物的全身毒性。这些发现对于未来生产具有更高疗效和安全性的超长效局部麻醉药制剂可能是有前景的。
