CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor that\nis being developed for dyslipidemia. Even though CKD-519 has shown potent CETP inhibition,\nthe exposure of CKD-519 was highly varied, depending on food and dose. For highly variable\nexposure drugs, it is crucial to use modeling and simulation to plan proper dose selection. This study\naimed to develop population pharmacokinetic (PK) and pharmacodynamics (PD) models of CKD-519\nand to predict the proper dose of CKD-519 to achieve target levels for HDL-C and LDL-C using results\nfrom multiple dosing study of CKD-519 with a standard meal for two weeks in healthy subjects.\nThe results showed that a 3-compartment with Erlangâ??s distribution, followed by the first-order\nabsorption, adequately described CKD-519 PK, and the bioavailability, which decreased by dose and\ntime was incorporated into the model (NONMEM version 7.3). After the PK model development,\nthe CETP activity and cholesterol (HDL-C and LDL-C) levels were sequentially modeled using the\nturnover model, including the placebo eect. According to PK-PD simulation results, 200 to 400 mg\nof CKD-519 showing a 40% change in HDL-C and LDL-C from baselines was recommended for proof\nof concept studies in patients with dyslipidemia.
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