Effects of intravenous bolus injection of emulsified isoflurane on QTc interval of healthy volunteers in Pharmacokinetics study

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 timepointsafter 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.