PMID- 34103898
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20221207
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 15
DP  - 2021
TI  - Pharmacokinetics, Tolerability and Pharmacogenetics of DA-8031 After Multiple 
      Ascending Doses in Healthy Male Subjects.
PG  - 2375-2384
LID - 10.2147/DDDT.S309763 [doi]
AB  - PURPOSE: DA-8031 is a novel selective serotonin reuptake inhibitor for the 
      treatment of premature ejaculation. This study investigated the pharmacokinetics, 
      safety and tolerability of multiple oral doses of DA-8031. In addition, a genetic 
      analysis was explored to evaluate the effect of genetic polymorphisms on the 
      pharmacokinetics of DA-8031. SUBJECTS AND METHODS: A dose block-randomized, 
      double-blind, placebo-controlled study was conducted in 3 dose groups with 20, 30 
      and 40 mg of DA-8031. Healthy male subjects were randomized to DA-8031 or placebo 
      at a 4:1 ratio in each dose group of 10 subjects by oral administration once 
      daily for 7 consecutive days. Serial blood and urine samples were collected for 
      the pharmacokinetic evaluation, and the pharmacokinetic-related genes were 
      analyzed by DMET(TM) plus. A safety evaluation was conducted including adverse 
      events (AEs) monitoring and 12-lead electrocardiogram (ECG). RESULTS: The plasma 
      DA-8031 concentration reached the maximum concentration (C(max)) in 2.2 to 3.0 h 
      and was eliminated with a mean half-life of 25.5 to 26.7 h at steady state. The 
      accumulation index of DA-8031 ranged 2.3 to 2.8. The systemic exposure of DA-8031 
      of the CYP2D6 intermediate metabolizer (IM) was significantly higher compared to 
      the CYP2D6 poor metabolizer (PM). There were no clinically significant QTc 
      interval changes, and all the adverse events were mild. CONCLUSION: After 
      multiple oral doses of DA-8031 20, 30, and 40 mg in this study, the systemic 
      exposure of DA-8031 increased in a more than dose-proportional manner with the 
      increasing doses, and DA-8031 was generally well tolerated. In addition, the 
      genetic polymorphisms of CYP2D6 have an impact on the pharmacokinetics of 
      DA-8031.
CI  - (c) 2021 Hwang et al.
FAU - Hwang, Sejung
AU  - Hwang S
AUID- ORCID: 0000-0003-0154-5777
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Lee, Dae Young
AU  - Lee DY
AD  - Drug Metabolism and Pharmacokinetics (DMPK), Drug Evaluation, Dong-A ST Research 
      Institute, Gyonggi-do, Republic of Korea.
FAU - Cho, Joo-Youn
AU  - Cho JY
AUID- ORCID: 0000-0001-9270-8273
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Chung, Jae-Yong
AU  - Chung JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
FAU - Jang, In-Jin
AU  - Jang IJ
AUID- ORCID: 0000-0002-8384-3139
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AUID- ORCID: 0000-0003-0921-7225
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Lee, SeungHwan
AU  - Lee S
AUID- ORCID: 0000-0002-1713-9194
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20210601
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Benzofurans)
RN  - 0 (DA 8031)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Benzofurans/administration & dosage/blood/*pharmacokinetics
MH  - Cytochrome P-450 CYP2D6/genetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Tolerance
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Genetic/drug effects/genetics
MH  - Selective Serotonin Reuptake Inhibitors/administration & 
      dosage/blood/*pharmacokinetics
MH  - Young Adult
PMC - PMC8179755
OTO - NOTNLM
OT  - clinical pharmacology
OT  - pharmacogenomics
OT  - phase 1 study
OT  - selective serotonin reuptake inhibitors
COIS- All authors report no conflicts of interest regarding the publication of this 
      manuscript.
EDAT- 2021/06/10 06:00
MHDA- 2021/11/30 06:00
PMCR- 2021/06/01
CRDT- 2021/06/09 06:40
PHST- 2021/03/08 00:00 [received]
PHST- 2021/04/22 00:00 [accepted]
PHST- 2021/06/09 06:40 [entrez]
PHST- 2021/06/10 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2021/06/01 00:00 [pmc-release]
AID - 309763 [pii]
AID - 10.2147/DDDT.S309763 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2021 Jun 1;15:2375-2384. doi: 10.2147/DDDT.S309763. 
      eCollection 2021.