Yoon Sumin, Yi Sojeong, Rhee Su-Jin, Lee Hyun A, Kim Yun, Yu Kyung-Sang, Chung Jae-Yong
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea.
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam 13620, Republic of Korea.
Transl Clin Pharmacol. 2019 Sep;27(3):107-114. doi: 10.12793/tcp.2019.27.3.107. Epub 2019 Sep 30.
This study aimed to assess the pharmacokinetics of cyclosporine A (CsA) in Asian children with renal impairment (RI) by developing a physiologically-based pharmacokinetic (PBPK) model with Simcyp Simulator. The PBPK model of Asian children with RI was developed by modifying the physiological parameters of the built-in population libraries in Simcyp Simulator. The ratio of healthy and RI populations was obtained for each parameter showing a difference between the populations. Each ratio was multiplied by the corresponding parameter in healthy Asian children. The model verification was performed with published data of Korean children with kidney disease given multiple CsA administrations. Simulations were performed with different combinations of ethnicity, age, and renal function to identify the net impact of each factor. The simulated results suggested that the effect of RI was higher in children than adults for both Caucasian and Asian. In conclusion, the constructed model adequately characterized CsA pharmacokinetics in Korean children with RI. Simulations with populations categorized by ethnicity, age, and renal function enabled to assess the net impact of each factor on specific populations.
本研究旨在通过使用Simcyp模拟器开发基于生理的药代动力学（PBPK）模型，评估环孢素A（CsA）在亚洲肾功能损害（RI）儿童中的药代动力学。通过修改Simcyp模拟器中内置人群库的生理参数，建立了亚洲RI儿童的PBPK模型。获得了每个在健康人群和RI人群之间存在差异的参数的比值。将每个比值乘以健康亚洲儿童的相应参数。利用韩国肾病儿童多次给予CsA的已发表数据进行模型验证。采用不同的种族、年龄和肾功能组合进行模拟，以确定各因素的综合影响。模拟结果表明，无论是白种人还是亚洲人，儿童RI的影响都高于成人。总之，所构建的模型充分表征了韩国RI儿童中CsA的药代动力学。按种族、年龄和肾功能对人群进行模拟能够评估各因素对特定人群的综合影响。
