Foster R H, Markham A
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 2000 Mar;59(3):551-79. doi: 10.2165/00003495-200059030-00013.
Based on findings that the cardiotoxicity infrequently observed with racemic bupivacaine shows enantioselectivity, i.e. it is more pronounced with the R(+)-enantiomer, the S(-)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic. The majority of in vitro, in vivo and human pharmacodynamic studies of nerve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicity than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75 mg, produced less prolongation of the QTc interval than bupivacaine. Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine. Levobupivacaine is long acting with a dose-dependent duration of anaesthesia. The onset of action is < or = 15 minutes with various anaesthetic techniques. In studies of surgical anaesthesia in adults, levobupivacaine provided sensory block for up to 9 hours after epidural administration of < or = 202.5 mg, 6.5 hours after intrathecal 15 mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blind clinical studies established that the anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those of bupivacaine at the same dose. Sensory block tended to be longer with levobupivacaine than bupivacaine, amounting to a difference of 23 to 45 minutes with epidural administration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block. Conditions satisfactory for surgery and good pain management were achieved by use of local infiltration or peribulbar administration of levobupivacaine. Levobupivacaine was generally as effective as bupivacaine for pain management during labour, and was effective for the management of postoperative pain, especially when combined with clonidine, morphine or fentanyl. The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. No clinically significant ECG abnormalities or serious CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%).
Levobupivacaine is a long acting local anaesthetic with a clinical profile closely resembling that of bupivacaine. However, current preclinical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are needed before the role of the drug can be fully established. Excluding pharmacoeconomic considerations, levobupivacaine is an appropriate choice for use in place of bupivacaine.
基于外消旋布比卡因很少观察到的心脏毒性具有对映体选择性这一发现，即R(+)-对映体更为明显，已开发出S(-)-对映体（左旋布比卡因）作为长效局部麻醉药用于临床。大多数关于神经阻滞的体外、体内及人体药效学研究表明，左旋布比卡因的效能与布比卡因相似。然而，在动物研究中，左旋布比卡因的心血管和中枢神经系统毒性风险低于布比卡因。在人体志愿者中，左旋布比卡因的负性肌力作用较小，静脉注射剂量>75mg时，其QTc间期延长程度小于布比卡因。左旋布比卡因引起的脑电图上提示中枢神经系统抑制的变化较少。左旋布比卡因作用时间长，麻醉持续时间呈剂量依赖性。采用各种麻醉技术时，起效时间≤15分钟。在成人外科麻醉研究中，硬膜外给予≤202.5mg左旋布比卡因后感觉阻滞可达9小时，鞘内注射15mg后可达6.5小时，臂丛阻滞给予2mg/kg后可达17小时。随机双盲临床研究证实，相同剂量下左旋布比卡因的麻醉和/或镇痛效果与布比卡因基本相似。左旋布比卡因的感觉阻滞往往比布比卡因持续时间长，硬膜外给药相差23至45分钟，周围神经阻滞相差约2小时。硬膜外给药时，左旋布比卡因引起的运动阻滞延长程度小于感觉阻滞。周围神经阻滞未观察到这种差异。通过局部浸润或球周给药使用左旋布比卡因可达到满意的手术条件和良好的疼痛管理。在分娩期间疼痛管理方面，左旋布比卡因通常与布比卡因效果相同，对术后疼痛管理也有效，尤其是与可乐定、吗啡或芬太尼合用时。在临床试验中，左旋布比卡因和布比卡因的耐受性特征非常相似。所用剂量未出现具有临床意义的心电图异常或严重中枢神经系统事件。与左旋布比卡因治疗相关的最常见不良事件是低血压（31%）。
左旋布比卡因是一种长效局部麻醉药，其临床特征与布比卡因非常相似。然而，目前临床前安全性和毒性数据显示左旋布比卡因优于布比卡因。在该药物的作用完全明确之前，需要有将左旋布比卡因与罗哌卡因进行比较的临床数据。排除药物经济学因素，左旋布比卡因是替代布比卡因使用的合适选择。
