PMID- 24417786
OWN - NLM
STAT- MEDLINE
DCOM- 20141104
LR  - 20141120
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 36
IP  - 1
DP  - 2014 Jan 1
TI  - Effects of ketoconazole on the pharmacokinetic properties of CG100649, a novel 
      NSAID: a randomized, open-label crossover study in healthy Korean male 
      volunteers.
PG  - 115-25
LID - S0149-2918(13)01119-3 [pii]
LID - 10.1016/j.clinthera.2013.12.004 [doi]
AB  - BACKGROUND: CG100649, a novel selective cyclooxygenase-2 inhibitor that also 
      inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk 
      typical of other NSAIDs. Concurrent medications may influence the activities of 
      the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized. 
      OBJECTIVES: This study was designed to evaluate the influence of ketoconazole, a 
      known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649. 
      METHODS: This randomized, open-label, 2 x 2 crossover study was conducted in 
      healthy Korean male volunteers. Each subject received the following 2 treatments 
      in a randomly allocated sequence, separated by a washout period of 42 days: 
      single oral dose of CG100649 6 mg, and concurrent dosing of CG100649 6 mg and 
      ketoconazole 400 mg followed by ketoconazole 400 mg/d over 4 days. Blood samples 
      for pharmacokinetic analysis were collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 
      6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 240, 384, and 480 hours after dosing 
      of CG100649 in each sequence. Tolerability assessments were performed throughout 
      the study. RESULTS: Thirty subjects participated, and 26 subjects completed the 
      study. Seventeen adverse events (AEs) were reported in 10 subjects, and all AEs 
      were recovered without any sequelae. No serious AEs were reported. Six subjects 
      receiving the single dose of CG100649 had 9 AEs, and 7 subjects receiving the 
      combination of ketoconazole and CG100649 had 8 AEs. The Cmax of CG100649 with 
      CG100649 only and with concurrent administration of CG100649 + ketoconazole were 
      similar (10.7 and 11.0 ng/mL, respectively). The CG100649 AUClast with concurrent 
      ketoconazole was 1.29-fold greater than that with CG100649 only (2074.0 and 
      2685.8 ng . h/mL) and demonstrated a statistically significant difference (P < 
      0.05). However, there were no statistically significant differences in vital 
      signs, clinical laboratory test results, ECGs, or AEs between treatments. 
      CONCLUSION: Although the AUC of CG100649 increased by 29% with the concurrent 
      medication of ketoconazole, it is considered that concurrent administration of 
      CG100649 with ketoconazole would not change the safety profile of CG100649.
CI  - Copyright (c) 2014 Elsevier HS Journals, Inc. All rights reserved.
FAU - Youn Choi, Hee
AU  - Youn Choi H
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Jin, Seok-Joon
AU  - Jin SJ
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Jung, Jin Ah
AU  - Jung JA
AD  - Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 
      Seoul, Republic of Korea.
FAU - Kim, Un-Jib
AU  - Kim UJ
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Ko, Young-Ju
AU  - Ko YJ
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Noh, Yook-Hwan
AU  - Noh YH
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Bae, Kyun-Seop
AU  - Bae KS
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea.
FAU - Lim, Hyeong-Seok
AU  - Lim HS
AD  - Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, 
      Republic of Korea; University of Ulsan College of Medicine, Seoul, Republic of 
      Korea. Electronic address: mdhslim@gmail.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01154764
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 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cytochrome P-450 CYP3A Inhibitors)
RN  - R9400W927I (Ketoconazole)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Carbonic Anhydrase Inhibitors/administration & dosage/*adverse 
      effects/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Cyclooxygenase 2 Inhibitors/administration & dosage/*adverse 
      effects/*pharmacokinetics
MH  - *Cytochrome P-450 CYP3A Inhibitors
MH  - Drug Administration Schedule
MH  - Drug Synergism
MH  - Humans
MH  - Ketoconazole/administration & dosage/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Young Adult
OTO - NOTNLM
OT  - CG100649
OT  - COX-2 inhibitor
OT  - drug interaction
OT  - ketoconazole
OT  - pharmacokinetic
EDAT- 2014/01/15 06:00
MHDA- 2014/11/05 06:00
CRDT- 2014/01/15 06:00
PHST- 2013/07/22 00:00 [received]
PHST- 2013/11/07 00:00 [revised]
PHST- 2013/12/06 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
AID - S0149-2918(13)01119-3 [pii]
AID - 10.1016/j.clinthera.2013.12.004 [doi]
PST - ppublish
SO  - Clin Ther. 2014 Jan 1;36(1):115-25. doi: 10.1016/j.clinthera.2013.12.004.