PMID- 27357738
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20220330
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 116
IP  - 3
DP  - 2016 Aug 30
TI  - Safety, tolerability and clinical pharmacology of dabigatran etexilate in 
      adolescents. An open-label phase IIa study.
PG  - 461-71
LID - 10.1160/TH15-04-0275 [doi]
AB  - Venous thromboembolism (VTE) incidence is increasing among children owing to many 
      factors, including improved diagnosis of VTE. There is a need for alternative 
      treatment options. Our objective was to investigate the safety, pharmacokinetics 
      (PK) and pharmacodynamics (PD) of dabigatran etexilate in adolescents with VTE. 
      Adolescents aged 12 to <18 years (n = 9) who successfully completed planned 
      treatment for primary VTE were administered dabigatran etexilate twice daily for 
      three days; initially 1.71 (+/- 10 %) mg/kg (80 % of a 150 mg/70 kg twice daily 
      adult dose), followed by 2.14 (+/- 10 %) mg/kg (target adult dose adjusted for 
      patient's weight), if there were no safety concerns. No bleeding events, deaths 
      or drug-related serious adverse events (AEs) were reported; three 
      treatment-emergent AEs, all gastrointestinal-related, occurred in two patients. 
      In these adolescent patients with normal renal function, presumed steady-state 
      trough plasma concentrations of dabigatran were low (geometric mean 
      dose-normalised total dabigatran plasma concentration: 0.493 ng/ml/mg at 72 
      hours). Total dabigatran concentrations were well predicted by the RE-LY(R) 
      population PK model (94 % of trough concentrations were within the 80 % 
      prediction interval). The relationship between total dabigatran plasma 
      concentration, diluted thrombin time and ecarin clotting time (ECT) was linear; 
      the relationship with activated partial thromboplastin time (aPTT) was 
      non-linear. Adult population PK/PD models predicted the adolescent 
      concentration-ECT and -aPTT relationships well. In conclusion, dabigatran 
      etexilate was generally well tolerated, except for occurrence of dyspepsia in two 
      patients, over the three-day treatment period. The dabigatran PK/PD relationship 
      observed in adolescent patients was similar to that in adult patients.
FAU - Halton, Jacqueline M L
AU  - Halton JM
AD  - Jacqueline Halton, Children's Hospital of Eastern Ontario, Ottawa, Ontario, 
      Canada, Tel.: +1 613 737 7600, Fax: +1 613 738 4828, E-mail: halton@cheo.on.ca.
FAU - Lehr, Thorsten
AU  - Lehr T
FAU - Cronin, Lisa
AU  - Cronin L
FAU - Lobmeyer, Maximilian T
AU  - Lobmeyer MT
FAU - Haertter, Sebastian
AU  - Haertter S
FAU - Belletrutti, Mark
AU  - Belletrutti M
FAU - Mitchell, Lesley G
AU  - Mitchell LG
LA  - eng
SI  - ClinicalTrials.gov/NCT00844415
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20160630
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antithrombins)
RN  - 0 (Prodrugs)
RN  - I0VM4M70GC (Dabigatran)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Antithrombins/adverse effects/pharmacokinetics/*pharmacology
MH  - Dabigatran/adverse effects/pharmacokinetics/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dyspepsia/chemically induced
MH  - Female
MH  - Humans
MH  - Male
MH  - Prodrugs/adverse effects/pharmacokinetics/pharmacology
MH  - Venous Thromboembolism/blood/*drug therapy
OTO - NOTNLM
OT  - Adolescent
OT  - anticoagulants
OT  - dabigatran
OT  - direct thrombin inhibitors
OT  - venous thromboembolism
EDAT- 2016/07/01 06:00
MHDA- 2018/01/30 06:00
CRDT- 2016/07/01 06:00
PHST- 2015/04/01 00:00 [received]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/07/01 06:00 [entrez]
PHST- 2016/07/01 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
AID - 15-04-0275 [pii]
AID - 10.1160/TH15-04-0275 [doi]
PST - ppublish
SO  - Thromb Haemost. 2016 Aug 30;116(3):461-71. doi: 10.1160/TH15-04-0275. Epub 2016 
      Jun 30.