Jung Yun Seob, Chae Dongwoo, Park Kyungsoo
Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea.
Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul 03722, Korea.
Transl Clin Pharmacol. 2018 Jun;26(2):93-98. doi: 10.12793/tcp.2018.26.2.93. Epub 2018 Jun 18.
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 ( ) inhibited by drug effects (Eff), which were represented by a sigmoid model [Eff = · / ( +γ)] with being maximum drug effect, drug plasma concentration at 50% of , C drug plasma concentrations, and γ the Hill coefficient. For the selected PD model, parameter estimates were 0.613 for , 0.192 for , 730 ng/ml for 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.
西洛他唑用于治疗间歇性跛行、溃疡和疼痛。本研究基于先前建立的药代动力学（PK）模型，旨在为健康韩国受试者建立西洛他唑闭合时间（CT）延长效应的群体药效学（PD）模型。PD数据来自2009年在延世大学Severance医院进行的一项研究中的29名健康受试者。所使用的PK模型是具有一级吸收的二室模型。CT数据最好用一个周转模型来描述，该模型具有一个受药物效应（Eff）抑制的分数周转率常数（ ），药物效应由一个S形模型[Eff = · / ( +γ)]表示，其中 为最大药物效应， 为 的50%时的药物血浆浓度，C为药物血浆浓度，γ为希尔系数。对于所选的PD模型，参数估计值为 时 为0.613 ， 为0.192， 为730 ng/ml，γ为5.137。性别和咖啡因饮用状况对基线CT有显著影响，男性非咖啡因饮用者的基线CT为85.36秒，女性和咖啡因饮用者分别增加了15.5%和16.4%。该模型充分描述了CT的时间进程。这是韩国人群中关于西洛他唑CT延长效应的第一项群体PD研究。
