Background: Ibutilide, a class Ⅲ antiarrhythmic agent, is primarily used for conversion of atrial flutter and fibrillation and is a good alternative to electrical cardioversion.However, ibutilide increases the duration and dispersion of ventricular repolarization and induces QT prolongation.Despite its efficacy, it is not widely used,mainly because of physician's lack of awareness about its safety and efficacy profile, and there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK/PDs) of ibutilide and ibutilide-induced QT prolongation.Objective: To characterize the relationship between plasma concentration of ibutilide and QTcF prolongation in healthy Chinese male subjects, thus promote the understanding of concentration-response of ibutilide and awareness about its safety and efficacy profile.Methods: Ibutilide plasma concentrations and QT interval data were obtained from previously published study of ibutilide, following 10-minute intravenous infusion: 0.005, 0.01, or 0.02 mg/kg, or 0.5, 0.75, or 1.0 mg.Data analysis was based on non-linear mixed effects modelling (NONMEM version7.2).The first-order conditional estimation method and the ADVAN6 subroutine were used to estimate parameters and variability.Covariate effects on parameters were investigated using stepwise forward inclusion and backward elimination.Results: The PK profiles of ibutilide was best described by a three-compartmental model, with a combined additive and proportional residual error model and a direct-response Emax model best described the relationship between the individual observed QTcF data and the individual predicted ibutilide data.Fitting the PK-PD model to the time course of QT prolongation showed that the model reproduces the dose-dependent profile of the QT prolongation.Visual Predictive Check (VPC) showed that the final model well-described ibutilide pharmacokinetics and pharmacodynamics, which were estimated with relatively good precision.Conclusions: Our investigation provides a population PK-PDs model to relate the observed QT prolongation effects of ibutilide to its actions at different concentrations.This will improve the study of ibutilide models of Torsades de pointes to better understand the safety and efficacy of ibutilide.