Center for Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
Blood Rev. 2022 May;53:100909. doi: 10.1016/j.blre.2021.100909. Epub 2021 Nov 16.
Thrombopoietin regulates platelet production through activation of the thrombopoietin receptor (TPO-R). TPO-R agonists (TPO-RAs) are available to treat thrombocytopenia in chronic immune thrombocytopenia (ITP), chronic liver disease (CLD) patients who are undergoing a procedure, severe aplastic anemia (SAA), and hepatitis C virus (HCV) infection. There are four TPO-RAs approved in the US and Europe: romiplostim (ITP), eltrombopag (ITP, SAA, HCV), avatrombopag (ITP, CLD), and lusutrombopag (CLD). It is important to understand pharmacological characteristics of these agents when evaluating treatment options. Avatrombopag interacts with the transmembrane domain of the TPO-RA and does not compete with endogenous thrombopoietin for TPO-R binding. Structural differences between avatrombopag and other TPO-RAs may impart differential downstream effects on cell signaling pathways, potentially resulting in clinically relevant differences in outcome. Avatrombopag has a favorable pharmacological profile with similar exposure in Japanese, Chinese, or Caucasian patients and no drug-drug interactions, food interactions, or potential for chelation.
血小板生成素通过激活血小板生成素受体（TPO-R）来调节血小板生成。血小板生成素受体激动剂（TPO-RAs）可用于治疗慢性免疫性血小板减少症（ITP）、正在接受手术的慢性肝病（CLD）患者、严重再生障碍性贫血（SAA）和丙型肝炎病毒（HCV）感染引起的血小板减少症。目前在美国和欧洲有四种 TPO-RAs 获得批准：罗米司亭（ITP）、艾曲波帕（ITP、SAA、HCV）、avatrombopag（ITP、CLD）和 lusutrombopag（CLD）。在评估治疗选择时，了解这些药物的药理学特征非常重要。avatrombopag 与 TPO-RA 的跨膜结构域相互作用，不会与内源性血小板生成素竞争 TPO-R 结合。avatrombopag 与其他 TPO-RAs 之间的结构差异可能会对细胞信号通路产生不同的下游影响，从而可能导致临床相关的结果差异。avatrombopag 具有良好的药理学特性，在日本、中国或高加索患者中的暴露情况相似，且不存在药物相互作用、食物相互作用或螯合作用的潜在风险。
