Pharmacokinetics and Hepatic Uptake of Eltrombopag, a Novel Platelet-Increasing Agent

@article{Takeuchi2011PharmacokineticsAH,
  title={Pharmacokinetics and Hepatic Uptake of Eltrombopag, a Novel Platelet-Increasing Agent},
  author={Kazuya Takeuchi and Tomoko Sugiura and Saki Umeda and Kazuki Matsubara and Masato Horikawa and Noritaka Nakamichi and David L. Silver and Norihisa Ishiwata and Yukio Kato},
  journal={Drug Metabolism and Disposition},
  year={2011},
  volume={39},
  pages={1088 - 1096}
}
Eltrombopag (ELT) is a novel thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. Previous reports indicate that ELT is mainly eliminated in the liver, although its pharmacokinetic profile has not yet been clarified in detail. The purpose of the present study is to investigate the overall elimination mechanism of ELT. After intravenous administration of ELT to rats, approximately 40% of unchanged ELT was excreted into the bile in 72 h, whereas less than 0.02… 
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26 Citations

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Citation Type

Interaction of Novel Platelet-Increasing Agent Eltrombopag with Rosuvastatin via Breast Cancer Resistance Protein in Humans
TLDR
BCRP in small intestine may be the major target for interaction between ELT and rosuvastatin in humans, and inhibition of OATP1B1 by ELT can only partially explain the clinically observed interaction with rosuVastatin.
Use of eltrombopag in thrombocytopenia of liver disease
TLDR
The role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use are discussed.
Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers
TLDR
These changes in exposure were not considered clinically meaningful as the dose of eltrombopag is adjusted using within-patient dose titration based on platelet counts.
Organic Cation Transporter 1 Is Responsible for Hepatocellular Uptake of the Tyrosine Kinase Inhibitor Pazopanib
TLDR
The present findings suggest that OCT1 is responsible for hepatic uptake of pazopanib, and has the potential for clinically relevant inhibition of human OCT1.
Eltrombopag for use in children with immune thrombocytopenia.
TLDR
Eltrombopag has also been approved for treating refractory severe aplastic anemia and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.
Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for a Rat Organic Anion Transporting Polypeptide 1B2–Mediated Interaction in Hepatic Transport
TLDR
It appears that the distribution of LB to the liver is mediated by the hepatic uptake of transporters such as rat OATP1B2, and carrier-mediated transport is involved in the liver-specific drug–drug interaction between LB and ATV in vivo.
Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis C Patients
TLDR
This model can be applied to optimize eltrombopag dosing in order to reduce the incidence of thrombocytopenia in HCV-infected patient receiving interferon-based therapy.
Effects of Probenecid on Hepatic and Renal Disposition of Hexadecanedioate, an Endogenous Substrate of Organic Anion Transporting Polypeptide 1B in Rats.
Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator.
TLDR
It is concluded that ELT is a powerful iron chelator that decreases cellular iron and further enhances iron mobilization when combined with clinically available chelators.
Organic anion-transporting polypeptides (OATPs/SLCOs)
TLDR
Species differences exist in OATP transporters, such that human hepatic OATPs are not orthologs to preclinical species e.g. the mouse, rat and dog, and should be taken into consideration when selecting probe substrates for in vitro evaluation of potential DDIs.
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References

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TLDR
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