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Pharmacokinetic, Pharmacodynamic, and Safety Profile of a New Cholesteryl Ester Transfer Protein Inhibitor in Healthy Human Subjects
Author(s) -
Wolk R,
Chen D,
Clark R W,
Mancuso J,
Barclay P L
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.120
Subject(s) - cholesterylester transfer protein , postprandial , endocrinology , triglyceride , pharmacokinetics , medicine , chemistry , apolipoprotein e , lipoprotein , pharmacodynamics , aldosterone , high density lipoprotein , cholesterol , pharmacology , disease , insulin
A new cholesteryl ester (CE) transfer protein (CETP) inhibitor (CP‐800,569) was evaluated. Doses of 30–1,800 mg were administered once daily to healthy subjects for 14 days. Serum CP‐800,569 levels increased, and CETP activity decreased, in a dose‐related manner. Serum levels of high‐density lipoprotein (HDL) increased (by a maximum of 156%), and those of low‐density lipoprotein (LDL) decreased (by a maximum of 47%). CP‐800,569 also had the effect of lowering postprandial triglyceride levels. Trough concentrations of apolipoprotein E (apoE) increased: the maximum increases were 89% for total plasma apoE and 280% for HDL apoE. By contrast, the postprandial increases in total plasma levels of apoE and non HDL apoE were either diminished by CP‐800,569 or reversed to decreases. CP‐800,569 was very well tolerated, with some nonserious gastrointestinal adverse events seen only with the 1,800‐mg dose. No changes in blood pressure (BP) were observed. The possible effects of higher CP‐800,569 doses on aldosterone and cortisol levels could not be excluded. The results of this study may be useful in CP‐800,569 dose selection. Clinical Pharmacology & Therapeutics (2009) 86 4, 430–437. doi: 10.1038/clpt.2009.120