title: Effects of intravenous bolus injection of emulsified isoflurane on QTc interval of healthy volunteers in Pharmacokinetics study.
abstract: Emulsified isoflurane is a novel intravenous anesthetic, which is a lipid emulsion of isoflurane. As some drugs have a QTc-prolongation effect which can increase a risk of arrhythmia, this study was to evaluate the effects of emulsified isoflurane on the QTc interval. This was a single-center, randomized, single-blind, non-comparative study. Subjects were randomly allocated to receive an intravenous bolus injection of 22.63, 38.26, or 49.73 mg/kg emulsified isoflurane, respectively. Standard 12-lead electrocardiograms were recorded before administration and at 28 timepoints after administration. Blood samples and the end-tidal isoflurane concentrations were collected for pharmacokinetic analysis. The primary target variable was the QTcF change from baseline at each time point. A two-sided 90% confidence interval (CI) was calculated for a QTcF change from baseline at each timepoint. The maximal 90% CIs of the mean QTcF from the baseline for 22.63, 38.26 and 49.73mg/kg emulsified isoflurane were 2.52-21.18 ms, 15.66-35.90 ms, and 17.65-40.71 ms, respectively. Non-significant relationship was observed between QTcF and the plasma concentration (or the end-tidal isoflurane concentration). Single intravenous dose of emulsified isoflurane of the anticipated therapeutic dose or supra-therapeutic doses was associated with a potential dose-dependent and non-concentration-related QTc-prolongation effect.
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China / Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China / Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007530:Isoflurane / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane