PMID- 27895466
OWN - NLM
STAT- MEDLINE
DCOM- 20170619
LR  - 20181113
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 10
DP  - 2016
TI  - Pharmacokinetics, pharmacodynamics and safety of CKD-519, a CETP inhibitor, in 
      healthy subjects.
PG  - 3763-3770
AB  - CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) 
      inhibitor being developed for the treatment of dyslipidemia to raise high-density 
      lipoprotein cholesterol. We investigated the safety, tolerability, 
      pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy 
      adult subjects. A randomized, double-blinded, placebo-controlled, single 
      ascending dose study was performed. Eight healthy subjects were enrolled in each 
      CKD-519 dose group (25, 50, 100, 200, or 400 mg) and randomized to CKD-519 (n=6) 
      or matching placebo (n=2). CKD-519 reached the maximum plasma concentration 
      (C(max)) at 5-6 h post-dose, and had a long terminal half-life ranging between 
      40-70 h. The area under the plasma concentration-time curve (AUC) and C(max) 
      increased with the dose, however, C(max) and AUC normalized by dose decreased 
      with each incremental dose. CETP activity decreased with dose, and the maximum 
      decrease (63%-83%) was observed at 6-8 h post-dose. A sigmoid E(max) model best 
      described the relationship between CKD-519 plasma concentrations and CETP 
      activity with an EC(50) of 17.3 ng/mL. Overall, 11 adverse events (AEs) were 
      observed. All AEs were mild or moderate in intensity, and resolved without any 
      complications. There were no clinically significant effects on blood pressure. In 
      conclusion, single doses of CKD-519 up to 400 mg were well tolerated and showed 
      potent inhibition of CETP activity.
FAU - Kim, Choon Ok
AU  - Kim CO
AD  - Department of Clinical Pharmacology, Severance Hospital, Yonsei University 
      College of Medicine, Seoul.
FAU - Oh, Eun Sil
AU  - Oh ES
AD  - Department of Pharmaceutical Medicines and Regulatory Science, Colleges of 
      Medicine and Pharmacy, Yonsei University, Incheon.
FAU - Choi, Chungam
AU  - Choi C
AD  - Department of Clinical Pharmacology, Severance Hospital, Yonsei University 
      College of Medicine, Seoul.
FAU - Kim, Yeonjoo
AU  - Kim Y
AD  - Chong Kun Dang Clinical Research, Chong Kun Dang Pharmaceutical Corp.
FAU - Lee, Sera
AU  - Lee S
AD  - Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corp.
FAU - Kim, Semi
AU  - Kim S
AD  - Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corp.
FAU - Park, Min Soo
AU  - Park MS
AD  - Department of Clinical Pharmacology, Severance Hospital, Yonsei University 
      College of Medicine, Seoul; Department of Pediatrics, Yonsei University College 
      of Medicine, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20161115
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (CETP protein, human)
RN  - 0 (CKD-519)
RN  - 0 (Cholesterol Ester Transfer Proteins)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Oxazoles)
SB  - IM
MH  - Adult
MH  - Biological Availability
MH  - Blood Pressure/drug effects
MH  - Cholesterol Ester Transfer Proteins/*antagonists & inhibitors/blood/metabolism
MH  - Cholesterol, HDL/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Hydrocarbons, Fluorinated/administration & dosage/pharmacokinetics
MH  - *Hypolipidemic Agents/adverse effects/pharmacokinetics
MH  - Inhibitory Concentration 50
MH  - Male
MH  - Middle Aged
MH  - Oxazoles/administration & dosage/pharmacokinetics
MH  - Single-Blind Method
MH  - Young Adult
PMC - PMC5117885
OTO - NOTNLM
OT  - CKD-519
OT  - cholesteryl ester transfer protein inhibitor
OT  - pharmacodynamics
OT  - pharmacokinetics
COIS- YJ Kim, S Lee, and S Kim are full time employees of Chong Kun Dang Pharmaceutical 
      Corp. The other authors report no conflicts of interest in this work.
EDAT- 2016/11/30 06:00
MHDA- 2017/06/20 06:00
PMCR- 2016/11/15
CRDT- 2016/11/30 06:00
PHST- 2016/11/30 06:00 [entrez]
PHST- 2016/11/30 06:00 [pubmed]
PHST- 2017/06/20 06:00 [medline]
PHST- 2016/11/15 00:00 [pmc-release]
AID - dddt-10-3763 [pii]
AID - 10.2147/DDDT.S120387 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2016 Nov 15;10:3763-3770. doi: 10.2147/DDDT.S120387. 
      eCollection 2016.