卡拉巴豆碱与舒更葡糖钠逆转非去极化神经肌肉阻滞剂的疗效比较
Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents.
作者信息
Haerter Friederike, Simons Jeroen Cedric Peter, Foerster Urs, Moreno Duarte Ingrid, Diaz-Gil Daniel, Ganapati Shweta, Eikermann-Haerter Katharina, Ayata Cenk, Zhang Ben, Blobner Manfred, Isaacs Lyle, Eikermann Matthias
机构信息
From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (F.H., J.C.P.S., I.M.D., D.D.-G., M.E.); Clinic of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany (U.F., M.B.); Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland (S.G., B.Z., L.I.); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (K.E.-H., C.A.); and Department of Anesthesia and Critical Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.E.).
出版信息
Anesthesiology. 2015 Dec;123(6):1337-49. doi: 10.1097/ALN.0000000000000868.
BACKGROUND
The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation.
METHODS
The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine.
RESULTS
In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate.
CONCLUSIONS
Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.
背景
作者通过结合和失活作用评估了卡拉巴丁2逆转非去极化神经肌肉阻滞剂（NMBA）的相对有效性。
方法
在体外（竞争结合试验和尿液分析）、离体（n = 34；膈神经半膈肌标本）和体内（n = 108；大鼠股四头肌）评估了药物逆转维库溴铵、罗库溴铵和顺式阿曲库铵诱导的神经肌肉阻滞（NMB）的剂量反应关系。在稳态深度NMB状态下，离体创建了卡拉巴丁、新斯的明或舒更葡糖的累积剂量反应曲线。在活体大鼠中，作者研究了受试药物在生理条件下逆转深度阻滞的剂量反应关系，并测量了尿液中排出的卡拉巴丁2的量。
结果
体外实验表明，卡拉巴丁2与罗库溴铵的结合亲和力是舒更葡糖的89倍（Ka = 3.4 × 10 M和Ka = 3.8 × 10 M-）。在没有代谢失活的情况下获得的尿液分析（质子核磁共振）、竞争结合试验和离体研究结果符合舒更葡糖和卡拉巴丁2与罗库溴铵的1:1结合比例。在活体大鼠中，卡拉巴丁2剂量依赖性且迅速地逆转了所有受试的NMBA。与舒更葡糖相比，卡拉巴丁2逆转维库溴铵和罗库溴铵的摩尔效价更高。卡拉巴丁2经肾脏排泄，且不影响血压或心率。
结论
卡拉巴丁2能更有效地逆转大鼠中由苄基异喹啉类和甾体类NMBA诱导的NMB，即比舒更葡糖更快。卡拉巴丁2经尿液排泄，且在大鼠中耐受性良好。
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