Söderberg Lars, Dyhre Henrik, Roth Bodil, Björkman Sven
Hospital Pharmacy, Malmö University Hospital, Sweden.
Anesthesiology. 2006 Jan;104(1):110-21. doi: 10.1097/00000542-200601000-00017.
The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action.
The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations.
The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects.
The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.
本研究的目的是开发稳定且易于注射的局部麻醉药脂质储存制剂，其中药物浓度可根据所需作用持续时间进行变化。
制剂中含有2.0%、5.0%、10%、20%、40%、60%、80%或100%的利多卡因和丙胺卡因碱的低共熔混合物，溶于中链甘油三酯中。以2.0%利多卡因：盐酸丙胺卡因溶液和99.5%乙醇作为对照，在大鼠中研究坐骨神经阻滞的持续时间和局部神经毒性。对20%和60%的制剂，研究局部麻醉药从给药部位的释放速率以及根据体外释放数据预测体内储存特性的可能性。
与2%水溶液相比，20%制剂使感觉性坐骨神经阻滞的持续时间延长了3倍，60%制剂使其延长了约180倍。使用80%和100%制剂时，所有动物在2周后仍表现出神经阻滞。20%制剂的体内局部麻醉药释放可根据体外数据大致预测，而60%制剂则不能。60%及以上的制剂和乙醇表现出神经毒性作用。
这些制剂的药学性质优于其他储存制剂。高百分比制剂显示出大鼠坐骨神经阻滞迄今报道的最长作用持续时间。使用高浓度局部麻醉药储存制剂替代乙醇或苯酚用于慢性疼痛的长期神经阻滞的可能性值得进一步研究。
