Population pharmacodynamics of cilostazol in healthy Korean subjects
Translational and Clinical Pharmacology
;
: 93-98, 2018.
Article
in English
| WPRIM
| ID: wpr-742400
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Plasma
/
Colon, Sigmoid
/
Ulcer
/
Caffeine
/
Drinking
/
Absorption
/
Healthy Volunteers
/
Intermittent Claudication
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Translational and Clinical Pharmacology
Year:
2018
Type:
Article
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