Yang Hui, Yin Qinqin, Huang Luying, Zhang Min, Zhang Xinxin, Sun Qirong, Liu Xuewei, Wang Qi, Yang Xi, Tan Lingcan, Ye Mao, Liu Jin
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2021 Mar 10;12:626307. doi: 10.3389/fphar.2021.626307. eCollection 2021.
Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane. In a single-center, single-dose, double-blinded, randomized, two-period crossover study, healthy volunteers received intravenous injection of 30 mg/kg of isoflurane with either previous formulation of emulsion isoflurane (PFEI) or new formulation of emulsion isoflurane (NFEI). Arterial and venous blood samples were obtained for geometric mean test/reference ratios of C, AUC, and AUC as well as their 90% confidence interval (CI90) as the primary outcome. The secondary outcomes were safety measurements such as vital signs, 12-lead electrocardiography, adverse effects, and laboratory tests; and anesthesia efficacy was assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score, bispectral index (BIS), and loss/recovery of eyelash reflex. 24 subjects were eligible, of which 21 completed the whole experiment (NFEI n = 21, PFEI n = 23). Arterial geometric mean test/reference ratios of C, AUC, and AUC were 104.50% (CI90 92.81%-117.65%), 108.23% (94.51%-123.96%), and 106.53% (93.94%∼120.80%), respectively. The most commonly seen adverse effects for NFEI and PFEI were injection pain (38.1% vs. 34.8%), hypotension (19.0% vs. 13.0%), apnea (14.3% vs. 17.4%), and upper airway obstruction (14.3% vs. 13.0%). No severe adverse effect was observed. The effectiveness of general anesthesia was similar between the two formulations. The CI90 of C, AUC, AUC, NFEI, and PFEI were within the range of 80%-125%, suggesting bioequivalence between NFEI and PFEI. The safety and anesthesia effectiveness were also similar.
乳化异氟烷是一种通过将异氟烷分子包裹于乳剂中获得的新型静脉全身麻醉药。乳剂配方已根据中国食品药品监督管理总局的最新规定进行了改进。本研究旨在比较新型与先前配方的异氟烷乳剂的生物等效性。在一项单中心、单剂量、双盲、随机、两周期交叉研究中，健康志愿者静脉注射30mg/kg异氟烷，使用的是先前配方的异氟烷乳剂（PFEI）或新型配方的异氟烷乳剂（NFEI）。采集动脉和静脉血样，以获得C、AUC以及AUC的几何平均试验/对照比值及其90%置信区间（CI90）作为主要指标。次要指标为安全测量，如生命体征、12导联心电图、不良反应及实验室检查；麻醉效果通过改良的观察者警觉/镇静评估（MOAA/S）评分、脑电双频指数（BIS）以及睫毛反射消失/恢复情况进行评估。24名受试者符合条件，其中21名完成了整个实验（NFEI组n = 21，PFEI组n = 23）。C、AUC以及AUC的动脉几何平均试验/对照比值分别为104.50%（CI90 92.81%-117.65%）、108.23%（94.51%-123.96%）和106.53%（93.94%∼120.80%）。NFEI和PFEI最常见的不良反应为注射痛（38.1%对34.8%）、低血压（19.0%对13.0%）、呼吸暂停（14.3%对17.4%）以及上呼吸道梗阻（14.3%对13.0%）。未观察到严重不良反应。两种配方的全身麻醉效果相似。NFEI和PFEI的C、AUC、AUC的CI90在80%-125%范围内，表明NFEI与PFEI具有生物等效性。安全性和麻醉效果也相似。
