PMID- 37898393
OWN - NLM
STAT- MEDLINE
DCOM- 20231222
LR  - 20231222
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 192
DP  - 2024 Jan 1
TI  - Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese 
      healthy volunteers: A randomized, double-blind, controlled phase I study.
PG  - 106621
LID - S0928-0987(23)00251-8 [pii]
LID - 10.1016/j.ejps.2023.106621 [doi]
AB  - BACKGROUND AND OBJECTIVE: (S)-oxiracetam is the major active enantiomer of 
      oxiracetam, which is being developed for dementia. This trial was designed to 
      evaluate the safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in 
      healthy Chinese volunteers. METHODS: A randomized, controlled, double-blind and 
      dose-escalation design was used in this Phase I trial, which consisted of a 
      single-ascending-dose (SAD) study (400-2000 mg) and a multiple-ascending-dose 
      (MAD) study (400-1600 mg). Blood, urine and feces samples were collected for 
      pharmacokinetic analysis. Safety was evaluated by monitoring adverse events 
      (AEs). RESULTS: AEs in both studies were mild or moderate in severity and 
      dose-independent. In the SAD study, no chiral transformation was observed. 55.03% 
      and 36.16% of (S)-oxiracetam was excreted unchanged in urine and feces, 
      respectively. Exposures exhibited dose-proportional increases over the range of 
      400 to 1600 mg but almost unchanged from 1600 to 2000 mg. (S)-oxiracetam was 
      absorbed rapidly, reaching a peak at 0.75-1.00 h, and t(1/2) was 6.12-6.60 h. 
      Food had no effect on AUC, but prolonged T(max) to 3.00 h. In the MAD study, 
      steady-state was observed on day 5. Mild accumulations were observed after 7 days 
      of repeated dosing. CONCLUSION: (S)-oxiracetam was safe and tolerated with 
      favorable pharmacokinetic profiles at all study doses, providing dosing evidence 
      for further efficacy evaluation.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Zhang, Ting
AU  - Zhang T
AD  - Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of 
      Chongqing medical university, Chongqing, 402760, China.
FAU - Tao, Yi
AU  - Tao Y
AD  - Department of Phase I Clinical Trial Ward, the First Affiliated Hospital of 
      Chongqing Medical University, Chongqing, 400016, China.
FAU - Pu, Junliang
AU  - Pu J
AD  - Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of 
      Chongqing medical university, Chongqing, 402760, China.
FAU - Zhu, Mingxue
AU  - Zhu M
AD  - Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of 
      Chongqing medical university, Chongqing, 402760, China.
FAU - Wan, Lei
AU  - Wan L
AD  - Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of 
      Chongqing medical university, Chongqing, 402760, China.
FAU - Tang, Chengyong
AU  - Tang C
AD  - Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of 
      Chongqing medical university, Chongqing, 402760, China. Electronic address: 
      tcyongwzj@163.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231028
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - P7U817352G (oxiracetam)
RN  - 0 (Pyrrolidines)
RN  - 0 (Nootropic Agents)
SB  - IM
MH  - Humans
MH  - Administration, Oral
MH  - Area Under Curve
MH  - China
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - East Asian People
MH  - *Pyrrolidines/pharmacokinetics
MH  - *Nootropic Agents/pharmacokinetics
OTO - NOTNLM
OT  - (S)-oxiracetam
OT  - Chiral inversion, food effect
OT  - Metabolic profile
OT  - Pharmacokinetics
OT  - Safety and tolerability
COIS- Declaration of Competing Interest All authors have no conflicts of interest that 
      are directly relevant to the content of this article.
EDAT- 2023/10/29 06:46
MHDA- 2023/12/22 06:42
CRDT- 2023/10/28 19:30
PHST- 2023/06/12 00:00 [received]
PHST- 2023/10/22 00:00 [revised]
PHST- 2023/10/22 00:00 [accepted]
PHST- 2023/12/22 06:42 [medline]
PHST- 2023/10/29 06:46 [pubmed]
PHST- 2023/10/28 19:30 [entrez]
AID - S0928-0987(23)00251-8 [pii]
AID - 10.1016/j.ejps.2023.106621 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2024 Jan 1;192:106621. doi: 10.1016/j.ejps.2023.106621. Epub 
      2023 Oct 28.