The role of Eltrombopag/Eltrombopag

Eltrombopag is a second-generation thrombopoietin receptor agonist that helps the patient's body make more platelets. It is mainly used to treat low platelets caused by chronic immune (idiopathic) thrombocytopenia (ITP) or chronic hepatitis C infection. It is also used in patients with severe aplastic anemia. Eltrombopag must be taken under the guidance of a physician. The purpose of treatment is not to normalize the platelet count, but to maintain it above the bleeding risk level (>50,000/mm3), thereby potentially avoiding reduction or interruption of other treatments.

Eltrombopagis aTPO-RA. Ligand-receptor binding activates Janus kinase/signal transducer and transcriptional signaling pathway activator, inducing the proliferation and differentiation of human bone marrow progenitor cells into megakaryocytes. The net effect is an increase in the number of circulating platelets. It appears that eltrombopag binds TPO-R at a location distant from the endogenous TPO binding site and initiates signal transduction through a different mechanism. Therefore, these two drugs may have additive (rather than competitive) effects on platelet production. Endogenous TPO appears to be seven to nine times more potent than eltrombopag.

It appears that the pharmacokinetics of eltrombopag (peak concentration 2-6 hours after oral administration; mean half-life >12 hours) are linear, such that it results in a dose-dependent increase in platelet proliferation and differentiation (higher doses are more effective and less safe). Eltrombopag should be taken at least 4 hours before or after taking antacids, dairy products, and multivitamin/mineral supplements, as these products chelate and therefore significantly reduce the systemic absorption of eltrombopag. Although the absolute oral bioavailability of eltrombopag in human subjects has not been fully determined, it is estimated to be at least 52%. Nearly all (99.9%) of absorbed eltrombopag is bound to plasma proteins in the circulation, primarily albumin.