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A Population Pharmacokinetic and Pharmacodynamic Model of CKD-519

 Choon Ok Kim  ;  Sangil Jeon  ;  Seunghoon Han  ;  Min Soo Park  ;  Dong-Seok Yim 
 PHARMACEUTICS, Vol.12(6) : 573, 2020-06 
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CETP activity ; CETP inhibitor ; CKD-519 ; HDL-C ; population PK-PD modeling
CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor that is being developed for dyslipidemia. Even though CKD-519 has shown potent CETP inhibition, the exposure of CKD-519 was highly varied, depending on food and dose. For highly variable exposure drugs, it is crucial to use modeling and simulation to plan proper dose selection. This study aimed to develop population pharmacokinetic (PK) and pharmacodynamics (PD) models of CKD-519 and to predict the proper dose of CKD-519 to achieve target levels for HDL-C and LDL-C using results from multiple dosing study of CKD-519 with a standard meal for two weeks in healthy subjects. The results showed that a 3-compartment with Erlang's distribution, followed by the first-order absorption, adequately described CKD-519 PK, and the bioavailability, which decreased by dose and time was incorporated into the model (NONMEM version 7.3). After the PK model development, the CETP activity and cholesterol (HDL-C and LDL-C) levels were sequentially modeled using the turnover model, including the placebo effect. According to PK-PD simulation results, 200 to 400 mg of CKD-519 showing a 40% change in HDL-C and LDL-C from baselines was recommended for proof of concept studies in patients with dyslipidemia.
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6. Others (기타) > Dept. of Clinical Pharmacology (임상시험센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Choon Ok(김춘옥) ORCID logo
Park, Min Soo(박민수) ORCID logo
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