Population Pharmacokinetic/Pharmacodynamics Modeling of Ibutilide in Chinese Healthy Volunteers and Patients With Atrial Fibrillation (AF) and/or Atrial Flutter (AFL).
Clin Ther
; 39(7): 1320-1335, 2017 Jul.
Article
in En
| MEDLINE
| ID: mdl-28624123
ABSTRACT
PURPOSE:
The goal of this study was to develop a population pharmacokinetic (PK) and PK/pharmacodynamics (PD) model for ibutilide, to evaluate the time course of its effect on QT interval in Chinese.METHODS:
The population PK and PK/PD model were developed using data from 40 Chinese healthy volunteers using nonlinear mixed-effects modeling, and the final population PK/PD model was applied on 100 patients with atrial fibrillation (AF) and/or atrial flutter (AFL).FINDINGS:
The PK parameters of ibutilide were best described by a 3-compartment model with first-order elimination. No statistically significant covariate was found for each PK model parameter. Individualized QT interval correction, by heart rate, was performed by a power model, and the circadian rhythm of QT intervals was described by 2 mixed-effect cosine functions. The QT interval data of ibutilide was well characterized by a sigmoid Emax model (E(C)=Emaxγ×Cγ/(EC50γ+Cγ)) with an effect compartment. The final PK/PD model was used to estimate individual parameters of patient data and found good predictions compared with healthy volunteers; AF and/or AFL patients had lower Emax and higher EC50. IMPLICATIONS A population PK and PK/PD model for ibutilide in healthy volunteers was developed and could well capture ibutilide's PK/PD characteristics. The final PK/PD model was applied on patients with AF and/or AFL successfully.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Atrial Fibrillation
/
Atrial Flutter
/
Sulfonamides
/
Anti-Arrhythmia Agents
/
Models, Biological
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Ther
Year:
2017
Document type:
Article