PMID- 37208866
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230524
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 11
IP  - 3
DP  - 2023 Jun
TI  - Effect of a high-fat and high-calorie food on the pharmacokinetics of a novel, 
      potent GABA analog HSK16149 in healthy subjects.
PG  - e01102
LID - 10.1002/prp2.1102 [doi]
LID - e01102
AB  - HSK16149 is a novel, potent gamma-aminobutyric acid (GABA) analog for the 
      treatment of neuropathic pain. The purpose of this study was to assess the effect 
      of a high-fat and high-calorie meal on the pharmacokinetics of HSK16149 in 
      healthy Chinese subjects. An open-label, two-period crossover design was applied 
      in this study. Twenty-six subjects were enrolled and were randomly divided into 
      two groups: a fasted-fed group and a fed-fasted group, with 13 subjects in each 
      group. Subjects took a single oral dose of 45 mg of HSK16149 under fasted or fed 
      conditions on Day 1 and Day 4. A series of blood samples were collected for PK 
      analysis. Safety was evaluated throughout the study by physical examinations, 
      clinical laboratory tests, 12-lead ECGs, vital signs, and adverse events (AEs). 
      The parameters AUC(0-infinity) , AUC(0-t) , and C(max) of HSK16149 were compared to 
      assess the bioequivalence of HSK16149 under fasted and fed conditions. The 
      geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) of AUC(0-t) 
      and AUC(0-infinity) under the fed condition compared with the fasted condition were 
      95.84% (91.94-99.90%) and 95.79% (91.89-99.84%), respectively, which were all 
      within the bioequivalent interval (80.00-125.00%). The GMR (90% CI) of C(max) 
      under the fed condition compared with the fasted condition was 66.04% 
      (59.45-73.36%), which was not within the bioequivalent range (80.00-125.00%). All 
      adverse events were transient and resolved. This study demonstrated that HSK16149 
      can be administered with or without food.
CI  - (c) 2023 The Authors. Pharmacology Research & Perspectives published by British 
      Pharmacological Society and American Society for Pharmacology and Experimental 
      Therapeutics and John Wiley & Sons Ltd.
FAU - Wu, Qingqing
AU  - Wu Q
AUID- ORCID: 0000-0003-4105-290X
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Zhu, Huijuan
AU  - Zhu H
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Song, Rong
AU  - Song R
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Zhang, Mengqi
AU  - Zhang M
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Li, Fangqiong
AU  - Li F
AD  - Haisco Pharmaceutical Group Co., Ltd., Chengdu, China.
FAU - Zeng, Weifang
AU  - Zeng W
AD  - Haisco Pharmaceutical Group Co., Ltd., Chengdu, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Jia, Jingying
AU  - Jia J
AUID- ORCID: 0000-0002-2492-3219
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Yu, Chen
AU  - Yu C
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
FAU - Liu, Yanmei
AU  - Liu Y
AD  - Drug Clinical Trial Center, Shanghai Xuhui Central Hospital, Shanghai, China.
AD  - Shanghai Engineering Research Center of Phase I Clinical Research & Quality 
      Consistency Evaluation for Drugs, Shanghai, China.
AD  - Shanghai Institute of Clinical Mass Spectrometry, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
SB  - IM
MH  - Humans
MH  - Healthy Volunteers
MH  - *Food-Drug Interactions
MH  - Therapeutic Equivalency
MH  - *Fasting
MH  - Biological Availability
PMC - PMC10199234
OTO - NOTNLM
OT  - HSK16149
OT  - food effect
OT  - healthy subjects
OT  - high-fat
OT  - pharmacokinetics
OT  - safety
EDAT- 2023/05/20 09:42
MHDA- 2023/05/22 06:42
PMCR- 2023/05/19
CRDT- 2023/05/20 01:22
PHST- 2023/03/14 00:00 [revised]
PHST- 2023/01/09 00:00 [received]
PHST- 2023/04/21 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/20 09:42 [pubmed]
PHST- 2023/05/20 01:22 [entrez]
PHST- 2023/05/19 00:00 [pmc-release]
AID - PRP21102 [pii]
AID - 10.1002/prp2.1102 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2023 Jun;11(3):e01102. doi: 10.1002/prp2.1102.