Population pharmacodynamics of cilostazol in healthy Korean subjects.

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 (Kout) inhibited by drug effects (Eff), which were represented by a sigmoid Emax model [Eff = Emax · Cγ / (EC50γ+Cγ)] with Emax being maximum drug effect, EC50 drug plasma concentration at 50% of Emax, C drug plasma concentrations, and γ the Hill coefficient. For the selected PD model, parameter estimates were 0.613 hr−1 for Kout, 0.192 for Emax, 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.