PMID- 23870608
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20181202
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 35
IP  - 7
DP  - 2013 Jul
TI  - The pharmacokinetics and safety of a fixed-dose combination of acetylsalicylic 
      acid and clopidogrel compared with the concurrent administration of 
      acetylsalicylic acid and clopidogrel in healthy subjects: a randomized, 
      open-label, 2-sequence, 2-period, single-dose crossover study.
PG  - 985-94
LID - S0149-2918(13)00267-1 [pii]
LID - 10.1016/j.clinthera.2013.05.015 [doi]
AB  - BACKGROUND: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid 
      (ASA) is used for the treatment of acute coronary syndrome. A combined 
      formulation of ASA and clopidogrel has been developed to provide dosing 
      convenience and improve adherence. OBJECTIVE: This study was designed to compare 
      the pharmacokinetic properties and safety profile of a fixed-dose combination 
      formulation of ASA and clopidogrel with concurrent administration of each agent 
      in healthy male Korean volunteers. METHODS: This single-dose, randomized, 
      open-label, 2-period crossover study was conducted in 64 healthy Korean 
      volunteers. Equal numbers of eligible participants were randomly assigned to 
      receive either the fixed-dose combination of ASA 100 mg and clopidogrel 75 mg or 
      the free combination of each agent followed by a 7-day washout period and then 
      administration of the alternate formulation. Serial blood samples were collected 
      immediately before and after dosing for 24 hours. The safety profile was 
      evaluated by using adverse events (AEs), which were assessed by physical 
      examination, vital signs, ECGs, clinical laboratory tests, and interviews. The 2 
      formulations were considered to be bioequivalent if the 90% CIs for the 
      log-transformed C(max) and AUC(0-last) values were within the predetermined range 
      of 0.8 to 1.25. RESULTS: Sixty-four volunteers (mean [SD] age, 27.51 [8.15] 
      years; weight, 68.55 [7.86] kg; height, 173.80 [5.94] cm) were enrolled, and 63 
      completed the study. For ASA, the 90% CIs for the geometric mean ratios of C(max) 
      and AUC(0-last) were 0.9483 to 1.1717 and 0.9946 to 1.1020, respectively. For 
      salicylic acid, the 90% CIs were 0.9614 to 1.0396 for C(max) and 0.9778 to 1.0163 
      for AUC(0-last). For clopidogrel, the 90% CIs were 0.9809 to 1.2562 for C(max) 
      and 0.9674 to 1.2073 for AUC(0-last). Six of the 20 AEs reported were drug 
      related: decreased hemoglobin levels (n = 2), fever (n = 1), and headache (n = 1) 
      with the test formulation and increased alanine aminotransferase levels (n = 1) 
      and dyspepsia (n = 1) with the reference formulation. All of the drug-related AEs 
      were transient and mild in severity. CONCLUSIONS: The fixed-dose combination of 
      ASA and clopidogrel 100 mg/75 mg did not meet the regulatory criteria for 
      bioequivalence as defined by the Korea Food and Drug Administration. Both 
      formulations were well tolerated in these healthy male Korean subjects. 
      ClinicalTrials.gov Identifier: NCT01448330.
CI  - Copyright (c) 2013 Elsevier HS Journals, Inc. All rights reserved.
FAU - Jung, Jin Ah
AU  - Jung JA
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Korea.
FAU - Kim, Tae-Eun
AU  - Kim TE
FAU - Kim, Jung-Ryul
AU  - Kim JR
FAU - Kim, Min-Ji
AU  - Kim MJ
FAU - Huh, Wooseong
AU  - Huh W
FAU - Park, Kyung-Mi
AU  - Park KM
FAU - Lee, Soo-Youn
AU  - Lee SY
FAU - Ko, Jae-Wook
AU  - Ko JW
LA  - eng
SI  - ClinicalTrials.gov/NCT01448330
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Drug Combinations)
RN  - A74586SNO7 (Clopidogrel)
RN  - OM90ZUW7M1 (Ticlopidine)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aspirin/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Clopidogrel
MH  - Cross-Over Studies
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Therapy, Combination/adverse effects
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Ticlopidine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - acetylsalicylic acid
OT  - clopidogrel
OT  - fixed-dose combination
OT  - healthy
OT  - pharmacokinetics
EDAT- 2013/07/23 06:00
MHDA- 2014/01/28 06:00
CRDT- 2013/07/23 06:00
PHST- 2013/02/15 00:00 [received]
PHST- 2013/05/07 00:00 [revised]
PHST- 2013/05/21 00:00 [accepted]
PHST- 2013/07/23 06:00 [entrez]
PHST- 2013/07/23 06:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
AID - S0149-2918(13)00267-1 [pii]
AID - 10.1016/j.clinthera.2013.05.015 [doi]
PST - ppublish
SO  - Clin Ther. 2013 Jul;35(7):985-94. doi: 10.1016/j.clinthera.2013.05.015.