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 nonconcentration-related QTc-prolongation effect.