PMID- 28803122
OWN - NLM
STAT- MEDLINE
DCOM- 20180302
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 39
IP  - 9
DP  - 2017 Sep
TI  - Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of 
      Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects.
PG  - 1799-1810
LID - S0149-2918(17)30827-5 [pii]
LID - 10.1016/j.clinthera.2017.07.038 [doi]
AB  - PURPOSE: Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia 
      treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets 
      of rosuvastatin/ezetimibe could increase patient compliance. The aim of this 
      study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of 
      rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as 
      separate tablets in healthy Korean volunteers. METHODS: This trial was a 
      randomized, open-label, single-dose, 2-way crossover study. The healthy subjects 
      received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or 
      co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each 
      period (periods 1 and 2), with a 14-day washout period. The blood samples for PK 
      analysis were collected predose and up to 96 hours after administration, and 
      safety was assessed throughout the study. FINDINGS: Sixty-four healthy Korean 
      subjects were enrolled, and 57 subjects completed the study. All subjects were 
      men and mean age was 28.52 +/- 5.93. The geometric least squares mean ratios 
      (test/reference) and 90% CIs of C(max) and AUC(0-last) were 101.54% 
      (94.03-109.65) and 97.71% (91.86-103.93) for rosuvastatin, 108.93% (98.55-120.40) 
      and 102.90% (96.72-109.47) for free ezetimibe, and 106.74% (98.18-116.05) and 
      104.24 % (99.53-109.17) for total ezetimibe. Twenty-four adverse events (AEs) 
      were reported in 22 subjects. Three cases were related to the study drugs; 2 
      cases were mild, and 1 case was severe. However, all AEs were resolved without 
      any sequelae. In addition, there were no serious AEs throughout the study. 
      IMPLICATIONS: The FDC tablet of rosuvastatin/ezetimibe was well tolerated and 
      resulted in comparable systemic exposure with co-administration of rosuvastatin 
      and ezetimibe. ClinicalTrials.gov identifier: NCT02941848.
CI  - Copyright (c) 2017 Elsevier HS Journals, Inc. All rights reserved.
FAU - Min, Kyoung Lok
AU  - Min KL
AD  - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of 
      Medicine and Pharmacy, Yonsei University, Incheon, South Korea.
FAU - Park, Min Soo
AU  - Park MS
AD  - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of 
      Medicine and Pharmacy, Yonsei University, Incheon, South Korea; Department of 
      Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, 
      Seoul, South Korea; Department of Pediatrics, Severance Hospital, Yonsei 
      University College of Medicine, Seoul, South Korea.
FAU - Jung, Jina
AU  - Jung J
AD  - Clinical Research Team, Hanmi Pharmaceutical Co, Ltd, Seoul, South Korea.
FAU - Chang, Min Jung
AU  - Chang MJ
AD  - Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of 
      Medicine and Pharmacy, Yonsei University, Incheon, South Korea; Department of 
      Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, 
      Yonsei University, Incheon, South Korea. Electronic address: delivery98@yuhs.ac.
FAU - Kim, Choon Ok
AU  - Kim CO
AD  - Department of Clinical Pharmacology, Severance Hospital, Yonsei University 
      College of Medicine, Seoul, South Korea. Electronic address: 
      mjchang@yonsei.ac.kr.
LA  - eng
SI  - ClinicalTrials.gov/NCT02941848
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170810
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Tablets)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - EOR26LQQ24 (Ezetimibe)
SB  - IM
MH  - Adult
MH  - Anticholesteremic Agents/administration & dosage/*adverse 
      effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - Ezetimibe/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Rosuvastatin Calcium/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Tablets
MH  - Young Adult
OTO - NOTNLM
OT  - ezetimibe
OT  - fixed-dose combination
OT  - pharmacokinetics
OT  - rosuvastatin
EDAT- 2017/08/15 06:00
MHDA- 2018/03/03 06:00
CRDT- 2017/08/14 06:00
PHST- 2017/04/06 00:00 [received]
PHST- 2017/07/13 00:00 [revised]
PHST- 2017/07/19 00:00 [accepted]
PHST- 2017/08/15 06:00 [pubmed]
PHST- 2018/03/03 06:00 [medline]
PHST- 2017/08/14 06:00 [entrez]
AID - S0149-2918(17)30827-5 [pii]
AID - 10.1016/j.clinthera.2017.07.038 [doi]
PST - ppublish
SO  - Clin Ther. 2017 Sep;39(9):1799-1810. doi: 10.1016/j.clinthera.2017.07.038. Epub 
      2017 Aug 10.