PMID- 22336488
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20161125
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 3
DP  - 2012 Mar
TI  - A randomized, open-label, 5-period, balanced crossover study to evaluate the 
      relative bioavailability of eltrombopag powder for oral suspension (PfOS) and 
      tablet formulations and the effect of a high-calcium meal on eltrombopag 
      pharmacokinetics when administered with or 2 hours before or after PfOS.
PG  - 699-709
LID - 10.1016/j.clinthera.2012.01.011 [doi]
AB  - BACKGROUND: Bioavailability of the tablet formulation of eltrombopag, an oral 
      thrombopoietin receptor agonist indicated for the treatment of chronic immune 
      thrombocytopenia, is reduced by chelation of polyvalent cations (eg, calcium). A 
      powder for oral suspension (PfOS) formulation has been developed for use in 
      pediatrics. OBJECTIVE: We aimed to assess the bioavailability of eltrombopag PfOS 
      relative to the tablet formulation and the effect of a high-calcium meal on PfOS 
      bioavailability. METHODS: In this single-dose, open-label, randomized-sequence, 
      crossover study, healthy subjects received 25 mg eltrombopag orally as a tablet 
      fasted and as PfOS fasted or with, 2 hours before, or 2 hours after a 
      high-calcium meal. Noncompartmental pharmacokinetic parameters were estimated 
      from plasma concentration-time data collected over 72 hours post-dose. 
      Tolerability was assessed by laboratory tests, physical examinations, and adverse 
      events (AEs). RESULTS: The 40 enrolled subjects included 22 males and 18 females 
      of white/European (60%) or African-American/African (40%) heritage with mean (SD) 
      (mininum, maximum) age of 34 (12) (19, 62) years, weight of 75 (12) (54, 101) kg, 
      and body mass index of 25.8 (2.9) (19.7, 30) kg/m(2). Plasma eltrombopag AUC(0-infinity) 
      was higher for the PfOS than the tablet (geometric least-squares mean ratio 
      [GMR]: 1.22; 90% CI: 1.08-1.38). Plasma eltrombopag AUC(0-infinity) was reduced when the 
      PfOS was administered with a high-calcium meal (GMR: 0.25; 90% CI: 0.224-0.287) 
      or 2 hours after a meal (GMR: 0.53; 90% CI: 0.470-0.601), and, to a lesser 
      extent, when administered 2 hours before a meal (GMR: 0.80; 90% CI: 0.711-0.908). 
      The absorption lag time and t((1/2)) did not differ between treatments; T(max) was 
      delayed 1 hour when the PfOS was dosed with a high-calcium meal. AEs were not 
      serious and mild or moderate in intensity. AEs reported in >1 subject included 
      headache (11 subjects; 27.5%), presyncope (3 subjects, 7.5%), and vomiting (2 
      subjects, 5%). No clinically significant trends in laboratory tests or vital 
      signs were observed. CONCLUSIONS: In a healthy adult volunteer population, 
      bioavailability of eltrombopag PfOS was greater than the tablet and was reduced 
      when administered with or 2 hours before or after a high-calcium meal; this 
      effect was attenuated with PfOS dosing 2 hours before the meal. Eltrombopag was 
      generally well tolerated.
CI  - Copyright A(c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Wire, Mary Beth
AU  - Wire MB
AD  - Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline Research and 
      Development, Five Moore Drive, 17.1356F.2B, Research Triangle Park, NC27709, USA. 
      mary.b.wire@gsk.com
FAU - Bruce, Jennifer
AU  - Bruce J
FAU - Gauvin, Jennifer
AU  - Gauvin J
FAU - Pendry, Carolyn J
AU  - Pendry CJ
FAU - McGuire, Sandra
AU  - McGuire S
FAU - Qian, Yanwen
AU  - Qian Y
FAU - Brainsky, Andres
AU  - Brainsky A
LA  - eng
SI  - ClinicalTrials.gov/NCT01072162
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120214
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Benzoates)
RN  - 0 (Hydrazines)
RN  - 0 (Powders)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Thrombopoietin)
RN  - 0 (Suspensions)
RN  - 0 (Tablets)
RN  - 143641-95-6 (MPL protein, human)
RN  - S56D65XJ9G (eltrombopag)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Benzoates/administration & dosage/blood/*pharmacokinetics/pharmacology
MH  - Biological Availability
MH  - Calcium/*metabolism
MH  - Cross-Over Studies
MH  - Female
MH  - *Food
MH  - *Food-Drug Interactions
MH  - Humans
MH  - Hydrazines/administration & dosage/blood/*pharmacokinetics/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Powders
MH  - Pyrazoles/administration & dosage/blood/*pharmacokinetics/pharmacology
MH  - Receptors, Thrombopoietin/agonists
MH  - Suspensions
MH  - Tablets
MH  - Time Factors
MH  - Young Adult
EDAT- 2012/02/18 06:00
MHDA- 2012/07/17 06:00
CRDT- 2012/02/17 06:00
PHST- 2012/01/06 00:00 [accepted]
PHST- 2012/02/17 06:00 [entrez]
PHST- 2012/02/18 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - S0149-2918(12)00013-6 [pii]
AID - 10.1016/j.clinthera.2012.01.011 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Mar;34(3):699-709. doi: 10.1016/j.clinthera.2012.01.011. Epub 
      2012 Feb 14.