Population pharmacodynamics of cilostazol in healthy Korean subjects
10.12793/tcp.2018.26.2.93
- Author:
Yun Seob JUNG
1
;
Dongwoo CHAE
;
Kyungsoo PARK
Author Information
1. Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea. kspark@yuhs.ac
- Publication Type:Original Article
- Keywords:
Cilostazol;
Closure time;
Population pharmacodynamic model;
Turnover model;
Sigmoid E(max) model
- MeSH:
Absorption;
Caffeine;
Colon, Sigmoid;
Drinking;
Female;
Healthy Volunteers;
Humans;
Intermittent Claudication;
Male;
Plasma;
Ulcer
- From:Translational and Clinical Pharmacology
2018;26(2):93-98
- CountryRepublic of Korea
- Language:English
-
Abstract:
Cilostazol is used for the treatment of intermittent claudication, ulceration and pain. This study was conducted to develop a population pharmacodynamic (PD) model for cilostazol's closure time (CT) prolongation effect in healthy Korean subjects based on a pharmacokinetic (PK) model previously developed. PD data were obtained from 29 healthy subjects who participated in a study conducted in 2009 at Severance Hospital. The PK model used was a two-compartment model with first order absorption. CT data were best described by a turnover model with a fractional turnover rate constant (K(out)) inhibited by drug effects (Eff), which were represented by a sigmoid E(max) model [Eff = E(max) · C(γ) / (EC₅₀(γ)+C(γ))] with E(max) being maximum drug effect, EC₅₀ drug plasma concentration at 50% of E(max), C drug plasma concentrations, and γ the Hill coefficient. For the selected PD model, parameter estimates were 0.613 hr⁻¹ for K(out), 0.192 for E(max), 730 ng/ml for EC₅₀ and 5.137 for γ. Sex and caffeine drinking status significantly influenced the baseline CT, which was 85.36 seconds in male non-caffeine drinkers and increased by 15.5% and 16.4% in females and caffeine drinkers, respectively. The model adequately described the time course of CT. This was the first population PD study for cilostazol's CT prolongation effect in a Korean population.
