中国临床药理学杂志2017，Vol.33Issue(13)：1212-1215,1232,5.DOI:10.13699/j.cnki.1001-6821.2017.13.013
伊布利特在中国健康受试者中的群体药代动力学和药效学研究
Population pharmacokinetics and pharmacodynamics studies of ibutilide in healthy Chinese subjects
摘要
Abstract
Objective To establish the population pharmacokinetic and pharmacokinetic models of ibutilide in healthy subjects,and to study the dose-exposure-drug effect relationship and variation of ibutilide in healthy subjects and to provide the basis for clinical practice of ibutilide.Methods A total of 40 healthy subjects were enrolled in this single-center,randomized,dose-escalation trial.13 plasma concentrations of ibutilide and 29 QT interval observations were collected from each subject.NONMEM 7.2 was used to establish and evaluate the pharmacokinetic and pharmacodynamic models.Results The pharmacokinetic model of ibutilide was best described by the three-compartment model with linear elimination,and the pharmacodynamic model was rationally characterized by the sigmoid Emax model.Goodness-of-fit (GOF) was validated by visual predictive check(VPC) and Bootstrap,which indicated that the population pharmacokinetic and pharmacodynamic models of ibutilide in healthy subjects were stable and reliable.Parameters with high confidence were obtained,and the individual variation of population pharmacodynamic parameters the exponent of the sigmoid equation (γ) and the maximum response of QT interval (Emax) were 133.50％ and 64.10％,respectively.Conclusion The population pharmacokinetic and pharmacodynamic models of ibutilide in healthy volunteers were established for the first time and the presence of ibutilide-sensitive and poor-response population were observed,which suggested the necessity of individualized administration for ibutilide.关键词
伊布利特/群体药代动力学/群体药效学/尖端扭转型室速Key words
ibutilide/population pharmacokinetics/population pharmacodynamics/torsades de pointes分类
医药卫生引用本文复制引用
曾芝俊,王莉,华潞,蒋娟娟,庞慧敏,黄一玲,李一石,田蕾..伊布利特在中国健康受试者中的群体药代动力学和药效学研究[J].中国临床药理学杂志,2017,33(13):1212-1215,1232,5.基金项目
科学技术部国家科技重大专项基金资助项目(2012ZX09303008-001) （2012ZX09303008-001）
