Population pharmacokinetic/pharmacodynamic modelling of nifekalant in healthy Chinese volunteers.
Nifekalant
PK/PD
QT interval
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
01 Aug 2020
01 Aug 2020
Historique:
received:
25
10
2019
revised:
11
05
2020
accepted:
19
05
2020
pubmed:
27
5
2020
medline:
22
6
2021
entrez:
27
5
2020
Statut:
ppublish
Résumé
Nifekalant is a class III antiarrhythmic drug, and its major adverse effect is prolongation of the QT interval. This study analysed data generated from a pharmacokinetic (PK) study to develop a population PK/pharmacodynamics (PD) model for describing the relationship between plasma concentrations and prolongation of the QT interval over time following intravenous administration of nifekalant. This open-labelled, phase I clinical study comprised two dose level groups of eight healthy Chinese volunteers. Concentrations of nifekalant in plasma samples collected at set time-points were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. A PK/PD model was constructed using a non-linear mixed-effects approach (Phoenix NLME 8.1). Furthermore, demographic covariates of the model were investigated and a concentration factor (Conc
Identifiants
pubmed: 32454129
pii: S0928-0987(20)30174-3
doi: 10.1016/j.ejps.2020.105385
pii:
doi:
Substances chimiques
Pyrimidinones
0
nifekalant
5VZ7GZM43E
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105385Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.