PMID- 19446149
OWN - NLM
STAT- MEDLINE
DCOM- 20090727
LR  - 20161125
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 4
DP  - 2009 Apr
TI  - Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy 
      adult subjects: two single-dose, open-label, randomized-sequence, crossover 
      studies.
PG  - 764-76
LID - 10.1016/j.clinthera.2009.04.010 [doi]
AB  - BACKGROUND: Eltrombopag is the first orally self-administered, small-molecule, 
      nonpeptide thrombopoietin receptor agonist for the treatment of chronic 
      idiopathic thrombocytopenic purpura. OBJECTIVE: The aim of these studies was to 
      assess the effect of food and antacids on the pharmacokinetic and safety profiles 
      of eltrombopag. METHODS: Two independent, single-dose, open-label, 
      randomized-sequence, crossover studies of oral eltrombopag were conducted in 
      healthy adult volunteers. The first study (study A) compared eltrombopag 50 mg 
      (tablets or capsules) administered in the fasted state or tablets with a 
      high-fat, high-calcium breakfast. The second study (study B) investigated 
      eltrombopag tablets (75 mg) administered in the fasted state; immediately after a 
      low-fat, low-calcium meal or a high-fat, low-calcium meal; 1 hour before a 
      high-fat, low-calcium meal; or with an antacid containing aluminum hydroxide and 
      magnesium carbonate. Vital signs were recorded and electrocardiogram and clinical 
      laboratory tests were performed at screening, within 24 hours before and within 
      48 hours after each dose of study medication. Symptom assessment was performed 
      and adverse events (AEs) were assessed previous to study drug administration 
      through follow-up in terms of severity and relationship to study medication. 
      RESULTS: In study A, 18 male subjects (mean age, 23.0 years; weight, 70.3 kg; 
      white race, 94.4%) who received a high-fat, high-calcium breakfast had reduced 
      bioavailability of eltrombopag in terms of AUC(0-infinity)) by 59% (geometric 
      mean ratio [GMR], 0.41; 90% CI, 0.36-0.46) and C(max) by 65% (GMR, 0.35; 90% CI, 
      0.30-0.41) compared with subjects in a fasted state. In study B, the 
      bioavailability in 26 subjects (14 male, 12 female; mean age, 35.6 years; weight, 
      76.0 kg; white race, 65.4%) was not significantly changed when administered with 
      food that was low in calcium, despite the fat content (GMRs ranged from 0.87-1.03 
      for AUC(0-infinity) and 0.85-1.01 for C(max) across the 3 studied meals). Mean 
      plasma AUC(0-infinity)) and C(max) values decreased by approximately 70% (GMR, 
      0.30; 90% CI, 0.24-0.36 for AUC(0-infinity)) and 0.24-0.38 for C(max)) when 
      administered with a metal cation-containing antacid. No serious AEs were reported 
      and all AEs were rated as mild to moderate in intensity. The most frequently 
      reported AE was headache (study A, 6.3%; study B, 12.0%-29.2%). CONCLUSIONS: 
      Concomitant administration of eltrombopag with high-calcium food or an antacid 
      containing aluminum and magnesium was associated with significantly reduced 
      systemic exposure, whereas low-calcium meals were not. A single dose of 
      eltrombopag was generally well tolerated in these healthy volunteers.
FAU - Williams, Daphne D
AU  - Williams DD
AD  - GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
FAU - Peng, Bin
AU  - Peng B
FAU - Bailey, Christine K
AU  - Bailey CK
FAU - Wire, Mary B
AU  - Wire MB
FAU - Deng, Yanli
AU  - Deng Y
FAU - Park, Jung Wook
AU  - Park JW
FAU - Collins, David A
AU  - Collins DA
FAU - Kapsi, Shiva G
AU  - Kapsi SG
FAU - Jenkins, Julian M
AU  - Jenkins JM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antacids)
RN  - 0 (Benzoates)
RN  - 0 (Calcium, Dietary)
RN  - 0 (Capsules)
RN  - 0 (Dietary Fats)
RN  - 0 (Drug Combinations)
RN  - 0 (Hydrazines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Thrombopoietin)
RN  - 0 (Tablets)
RN  - 0E53J927NA (magnesium carbonate)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
RN  - I38ZP9992A (Magnesium)
RN  - S56D65XJ9G (eltrombopag)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aluminum Hydroxide/pharmacology
MH  - Antacids/*pharmacology
MH  - Area Under Curve
MH  - Benzoates/administration & dosage/adverse effects/*pharmacokinetics
MH  - Biological Availability
MH  - Calcium, Dietary/pharmacology
MH  - Capsules
MH  - Cross-Over Studies
MH  - Dietary Fats/pharmacology
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Female
MH  - *Food-Drug Interactions
MH  - Humans
MH  - Hydrazines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Magnesium/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Pyrazoles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Receptors, Thrombopoietin/agonists
MH  - Tablets
MH  - Young Adult
EDAT- 2009/05/19 09:00
MHDA- 2009/07/28 09:00
CRDT- 2009/05/19 09:00
PHST- 2009/02/26 00:00 [accepted]
PHST- 2009/05/19 09:00 [entrez]
PHST- 2009/05/19 09:00 [pubmed]
PHST- 2009/07/28 09:00 [medline]
AID - S0149-2918(09)00119-2 [pii]
AID - 10.1016/j.clinthera.2009.04.010 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Apr;31(4):764-76. doi: 10.1016/j.clinthera.2009.04.010.