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

Clinical Therapeutics
Mary B WireAndres Brainsky

Abstract

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. 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. 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). 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-∞) was higher for the PfOS ...Continue Reading

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Citations

Sep 19, 2014·International Journal of Hematology·Caizheng Li, Li Zheng
May 7, 2016·Drugs·Celeste B BurnessKarly P Garnock-Jones
May 26, 2017·Basic & Clinical Pharmacology & Toxicology·Li ZhengAn-Bo Xiang
Mar 15, 2018·Clinical Pharmacology and Therapeutics·Mary B WireTaoufik Ouatas
Jul 23, 2018·British Journal of Clinical Pharmacology·Hanny Al-Samkari, David J Kuter
Sep 14, 2018·Science Translational Medicine·Yun-Ruei KaoBritta Will
Aug 10, 2017·Frontiers in Psychology·Thijs T WingelaarRob A van Hulst
Apr 10, 2015·British Journal of Clinical Pharmacology·Hannah K Batchelor, John F Marriott
Apr 23, 2019·Therapeutic Advances in Hematology·Hanny Al-Samkari, David J Kuter
Nov 26, 2020·Revista Española De Enfermedades Digestivas : Organo Oficial De La Sociedad Española De Patología Digestiva·María Luisa Lozano
Oct 24, 2020·Expert Opinion on Pharmacotherapy·Zain Mohammad VirkHanny Al-Samkari
Jul 27, 2021·Annals of Hematology·John D GraingerNichola Cooper

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