1. Effect of Hepatic or Renal Impairment on Eltrombopag Pharmacokinetics.
- Author
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Bauman, John W., Vincent, Carolyn T., Peng, Bin, Wire, Mary B., Williams, Daphne D., and Park, Jung Wook
- Subjects
ANALYSIS of variance ,BENZOATES ,CLINICAL trials ,COMPUTER software ,CONFIDENCE intervals ,GASTROINTESTINAL system ,HETEROCYCLIC compounds ,HIGH performance liquid chromatography ,KIDNEY function tests ,KIDNEY diseases ,LIVER ,LIVER diseases ,MASS spectrometry ,ORAL drug administration ,RESEARCH funding ,THROMBOCYTOPENIA ,DATA analysis - Abstract
Eltrombopag, an oral, small-molecule, nonpeptide thrombopoietin receptor agonist for the treatment of thrombocytopenia, is highly protein bound and primarily eliminated via metabolism in the liver and gastrointestinal tract. Single-dose eltrombopag pharmacokinetics were evaluated in participants with hepatic or renal impairment given possible changes in systemic exposure due to reduced plasma protein binding or reduced metabolism. All participants received a single 50-mg dose of eltrombopag. The adverse event profile was similar across groups, with headache, nausea, and back pain most frequently reported. Compared with healthy participants, participants with mild, moderate, or severe hepatic impairment had mean increases in AUC0-∞ of 41%, 93%, and 80%, and participants with mild, moderate, or severe renal impairment had mean decreases in AUC0-∞ of 32%, 36%, and 60%. There was high pharmacokinetic variability and significant overlap in exposures between participants with hepatic or renal impairment and healthy participants. Results suggest that patients with renal impairment may initiate eltrombopag with the standard 50-mg once-daily starting regimen, whereas patients with moderate or severe hepatic impairment should consider a lower 25-mg once-daily regimen. Patients with hepatic or renal impairment should be closely monitored for platelet response and safety, and eltrombopag doses should be adjusted accordingly. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
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