PMID- 36678630
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230202
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 16
IP  - 1
DP  - 2023 Jan 16
TI  - Evaluation of Safety, Tolerability and Pharmacokinetic Characteristics of SA001 
      and Its Active Metabolite Rebamipide after Single and Multiple Oral 
      Administration.
LID - 10.3390/ph16010132 [doi]
LID - 132
AB  - Dry eye disease (DED) is one of the most common eye diseases caused by multiple 
      factors. Rebamipide, which is currently used to treat peptic ulcer disease, was 
      shown to enhance secretory function and modulate inflammation in animal disease 
      models. Considering the pathophysiology of DED, SA001 was developed expecting 
      enhanced systemic exposure of rebamipide. Clinical trials to evaluate the safety, 
      tolerability and pharmacokinetic (PK) characteristics of SA001 and its active 
      metabolite rebamipide were conducted. After oral administration of SA001, blood 
      and urine samples were collected for PK analysis of SA001 and rebamipide. PK 
      parameters were compared between SA001 and conventional rebamipide (Bamedin((R))) 
      and also between fasted and fed. Safety and tolerability were evaluated 
      throughout the study based on adverse events (AEs), physical examinations, vital 
      signs, 12-lead electrocardiography and clinical laboratory tests. SA001 was 
      rapidly absorbed and quickly converted to rebamipide. The systemic exposure of 
      rebamipide was dose-proportional after single and multiple doses. The plasma 
      concentration of rebamipide after administration of SA001 was higher with a dose 
      adjusted AUC(last) and C(max) 2.20 and 5.45 times higher in the 240 mg dose group 
      and 4.73 and 11.94 times higher in the 600 mg dose group compared to conventional 
      rebamipide. The favorable PK and tolerability profiles support further clinical 
      development.
FAU - Bae, Sungyeun
AU  - Bae S
AUID- ORCID: 0000-0002-6584-9158
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul 03080, Republic of Korea.
FAU - Huh, Ki Young
AU  - Huh KY
AUID- ORCID: 0000-0002-1872-9954
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul 03080, Republic of Korea.
FAU - Oh, Jaeseong
AU  - Oh J
AUID- ORCID: 0000-0001-6275-8587
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul 03080, Republic of Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul 03080, Republic of Korea.
FAU - Kim, Anhye
AU  - Kim A
AUID- ORCID: 0000-0002-6622-8089
AD  - Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, 
      CHA University, Seongnam 13496, Republic of Korea.
AD  - Department of Biomedical Informatics, CHA University School of Medicine, CHA 
      University, Seongnam 13488, Republic of Korea.
AD  - Institute for Biomedical Informatics, CHA University School of Medicine, CHA 
      University, Seongnam 13488, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20230116
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC9862565
OTO - NOTNLM
OT  - Sjogren syndrome
OT  - bioavailability
OT  - dry eye syndrome
OT  - phase 1 clinical trials
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/22 06:01
PMCR- 2023/01/16
CRDT- 2023/01/21 01:49
PHST- 2022/11/16 00:00 [received]
PHST- 2023/01/09 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/01/21 01:49 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/22 06:01 [medline]
PHST- 2023/01/16 00:00 [pmc-release]
AID - ph16010132 [pii]
AID - pharmaceuticals-16-00132 [pii]
AID - 10.3390/ph16010132 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2023 Jan 16;16(1):132. doi: 10.3390/ph16010132.