PMID- 32474728
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20221207
IS  - 2107-0180 (Electronic)
IS  - 0378-7966 (Print)
IS  - 0378-7966 (Linking)
VI  - 45
IP  - 5
DP  - 2020 Oct
TI  - Pharmacokinetics and Safety of Dabigatran Etexilate after Single and Multiple 
      Oral Doses in Healthy Chinese Subjects.
PG  - 601-609
LID - 10.1007/s13318-020-00626-4 [doi]
AB  - BACKGROUND AND OBJECTIVE: Dabigatran etexilate is a non-vitamin K antagonist oral 
      anticoagulant (NOAC) that is used to prevent stroke and systemic embolism in 
      adults with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. 
      Pharmacokinetic data on this anticoagulant in Chinese subjects are limited. This 
      study aimed to provide further information on the pharmacokinetic profile of 
      dabigatran in healthy Chinese subjects, together with its safety profile. 
      METHODS: This was an open-label, single-centre, phase I study. Subjects were 
      randomized into 110 and 150 mg dabigatran etexilate treatment groups. Each 
      subject received 7 days of treatment: a single dose on day 1, no dose on days 
      2-3, and then multiple doses on days 4-10. Blood samples were collected to 
      analyze the pharmacokinetic profile of dabigatran. All adverse events (AEs) were 
      recorded. Routine clinical laboratory tests, a physical examination, vital signs, 
      and 12-lead electrocardiogram (ECG) measurements were performed. RESULTS: A total 
      of 28 subjects (14 males and 14 females) were randomized in this trial. The 
      plasma concentration of total dabigatran reached its maximum measured 
      concentration at a median time of 3-4 h from the dose of interest (either the 
      initial single dose on day 1 or the final dose on day 10) under fed conditions, 
      and declined with an elimination half-life of 10.7-10.9 h following the dose of 
      interest. There was a modest difference in pharmacokinetic profile between male 
      and female subjects. None of the subjects experienced a serious adverse event 
      (SAE) or an AE of moderate or severe intensity. The investigator reported that 17 
      of the 28 subjects had mild treatment-emergent AEs that resolved without any 
      concomitant treatment or intervention. No clinically significant changes in vital 
      signs or ECG parameters were observed. CONCLUSIONS: This study revealed the 
      pharmacokinetic characteristics and good safety profile of dabigatran in healthy 
      Chinese subjects.
FAU - Duan, Jingli
AU  - Duan J
AUID- ORCID: 0000-0001-5738-8366
AD  - Department of Pharmacy, Peking University Third Hospital, Peking, China. 
      duanjingli@pkuih.edu.cn.
AD  - Department of Pharmacy, Peking University International Hospital, No. 1 Life Park 
      Road, Life Science Park of Zhongguancun, Changping District, Peking, 102206, 
      China. duanjingli@pkuih.edu.cn.
FAU - Yang, Li
AU  - Yang L
AD  - Department of Pharmacy, Peking University Third Hospital, Peking, China.
FAU - Li, Haiyan
AU  - Li H
AD  - Department of Cardiovascular, Peking University Third Hospital, Peking, China.
FAU - Yamamura, Norio
AU  - Yamamura N
AD  - Department of Clinical Pharmacokinetics/Pharmacodynamics, Nippon Boehringer 
      Ingelheim Co., Ltd., Kobe, Japan.
FAU - Harada, Akiko
AU  - Harada A
AD  - Department of Clinical Pharmacokinetics/Pharmacodynamics, Nippon Boehringer 
      Ingelheim Co., Ltd., Kobe, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Antithrombins)
RN  - I0VM4M70GC (Dabigatran)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Antithrombins/*administration & dosage/adverse effects/pharmacokinetics
MH  - Asian People
MH  - Dabigatran/*administration & dosage/adverse effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Electrocardiography
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Young Adult
PMC - PMC7511473
COIS- NY and AH are employees of Nippon Boehringer Ingelheim Co., Ltd.. DJ was the 
      principal investigator of this trial. Both YL and LH participated in the clinical 
      study. The authors report no other conflicts of interest in this work.
EDAT- 2020/06/01 06:00
MHDA- 2021/07/03 06:00
PMCR- 2020/05/30
CRDT- 2020/06/01 06:00
PHST- 2020/06/01 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2020/06/01 06:00 [entrez]
PHST- 2020/05/30 00:00 [pmc-release]
AID - 10.1007/s13318-020-00626-4 [pii]
AID - 626 [pii]
AID - 10.1007/s13318-020-00626-4 [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 2020 Oct;45(5):601-609. doi: 
      10.1007/s13318-020-00626-4.