摘要
背景缓释剂型能够延长局麻药的镇痛效果并降低其血浆峰浓度，这使我们可以更加安全地使用较大剂量的局麻药，延长镇痛的作用时间。之前我们报道了一种主动载入多囊大囊泡（1argemultivesicularvesicles，LMVVs）的布比卡因（多囊脂质体布比卡因），并证明在动物和人体内可以使镇痛作用时间延长5倍以上。本研究中，我们给出多囊脂质体布比卡因在人体内的药物代谢动力学数据。方法健康志愿者皮下注射0．5％单纯布比卡因20ml，1周后，注射2％的多囊脂质体布比卡因20ml，进行前瞻性非盲法交叉对照研究。结果8例受试者被纳入研究，未观察到局麻药的主观不良反应。通过血浆浓度一时间曲线模型获得血浆峰浓度及达峰时间。两组血浆峰浓度无显著差异（单纯布比卡因与脂质体布比卡因的浓度分别为0．87±0．45μg／ml和0．83±0．34μg／ml，P=0．83，无显著性差异）。这些数值远远低于被公认的中毒血浆浓度，即2-4μg／ml。达峰时间在脂质制剂中延长7倍（262±149分钟与37．5±16分钟，P〈0．01）。结论尽管以新的脂质制剂形式注入的布比卡因总剂量增加至4倍，两组的布比卡因血浆峰浓度并无差异。脂质体布比卡因消除和向血浆再分布的延迟与此前报道的长效制剂缓释效应导致的药代动力学效应的延长是相符的。
BACKGROUND： Depot formulations prolong the analgesic effect of local anesthetics and reduce peak plas- ma drug concentration. This allows for safer administration of larger doses of local anesthetics, which further prolongs the du- ration of analgesic effect. We previously reported the development of large multivesicular vesicles （LMVVs） remotely loaded with bupivacaine （LMVV liposomal bupivacaine） and demonstrated a 〉5-fold prolongation of analgesic effect in animals and humans. In this study, we present pharmacokinetic data of LMW liposomal bupivacaine in humans. METHODS： Healthy volunteers received subcutaneous injections of 20 ml plain 0.5% bupivacaine and, 1 week later, 20 ml of 2% LMW liposom- al bupivacaine in a prospective, open-label, crossover, controlled study. RESULTS： Eight subjects were studied. No subjective side effects of local anesthetics were observed. The maximal plasma concentration and the time to achieve maximal plasma concentration were assessed by modeling plasma concentration - time profiles. Maximal plasma concentration was not signifi- cantly different between groups （0. 87 ±0. 45 μg/ml and 0. 83 ±0. 34μg/ml for plain and liposomal bupivacaine, respective- ly; P = not significant, 0. 83）. These values are well below the putative toxic plasma concentration of 2 to 4 μg/rnl. Time to a- chieve maximal plasma concentration was 7-fold greater for the liposomal preparation （262 ± 149minutes vs 37.5 ±16 minutes, P 〈 0. 01 ）. CONCLUSIONS： 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 pro- longed redistribution of liposomal bupivacaine to plasma is compatible with the depot-related slow-release effect leading tothe prolonged pharmacodynamic effect previously reported.
出处
《麻醉与镇痛》
2012年第1期89-95,共7页
Anesthesia & Analgesia
