Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers
Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers
复制标题
DOI：
10.1093/bja/aem402
复制
发表时间：
2008-03-01
影响因子：
9.8
通讯作者：
Foubert, L.
中科院分区：
文献类型：
--
作者：
Cammu, G.;De Kam, P. J.;Foubert, L.
背景。Sugammadex可迅速逆转罗库溴铵和维库溴铵引起的神经肌肉阻滞。探讨糖马德与罗库溴铵或维库溴铵合用对QT间期的影响，以避免麻醉干扰为佳。因此，本初步研究旨在探讨在麻醉和非麻醉的健康志愿者中，单次静脉注射sugammadex与罗库溴铵或维库溴铵的安全性、耐受性和血浆药代动力学。在这项I期研究中，12名受试者使用异丙酚/瑞芬太尼麻醉，并接受糖胺酮16、20或32 mg kg（-1）联合罗库溴铵1.2 mg kg（-1）或维库溴铵0.1 mg kg(-1)；4名受试者未麻醉，同时给予糖玛酮32 mg kg(-1)，罗库溴铵1.2 mg kg（-1）或维库溴铵0.1 mg kg(-1) （n=2次治疗）。通过麻醉受试者的TOF-Watch((R)) SX监测和非麻醉志愿者的临床试验评估神经肌肉功能。在不同时间点测定糖胺酮、罗库溴铵和维库溴铵的血药浓度。无严重不良事件（ae）报告。14名受试者在给药后报告了23例ae。轻度头痛、疲倦、感觉寒冷（应用部位）、口干、口腔不适、恶心、天冬氨酸转氨酶和γ -谷氨酰转移酶水平升高以及注射部位中度刺激被认为可能与研究药物有关。心电图及生命体征无临床相关变化。罗库溴铵/维库溴铵血药浓度下降速度快于糖合成组。单剂量给药sugammadex 16、20或32 mg kg（-1）联合罗库溴铵1.2 mg kg（-1）或维库溴铵0.1 mg kg（-1）耐受性良好，无残留神经肌肉阻滞的临床证据，证实这些组合可以安全地同时给药于非麻醉受试者。罗库溴铵和维库溴铵的血浆浓度下降速度快于糖马德，降低了神经肌肉阻滞发展的理论风险。
Background. Sugammadex rapidly reverses rocuronium- and vecuronium-induced neuromuscular block. To investigate the effect of combination of sugammadex and rocuronium or vecuronium on QT interval, it would be preferable to avoid the interference of anaesthesia. Therefore, this pilot study was performed to investigate the safety, tolerability, and plasma pharmacokinetics of single i.v. doses of sugammadex administered simultaneously with rocuronium or vecuronium to anaesthetized and non-anaesthetized healthy volunteers.Methods. In this phase I study, 12 subjects were anaesthetized with propofol/remifentanil and received sugammadex 16, 20, or 32 mg kg(-1) combined with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1); four subjects were not anaesthetized and received sugammadex 32 mg kg(-1) with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) (n=2 per treatment). Neuromuscular function was assessed by TOF-Watch((R)) SX monitoring in anaesthetized subjects and by clinical tests in non-anaesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points.Results. No serious adverse events (AEs) were reported. Fourteen subjects reported 23 AEs after study drug administration. Episodes of mild headache, tiredness, cold feeling (application site), dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma-glutamyltransferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium/vecuronium plasma concentrations declined faster than those of sugammadex.Conclusions. Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.