Fostamatinib is the first approved spleen tyrosine kinase inhibitor for chronic immune thrombocytopenia. This review summarizes the clinical development, pharmacokinetics, pharmacodynamics, drug–drug interactions, adverse events, and comprehensive analyses of fostamatinib. While integrating these findings, we discuss the fostering and improvement of fostamatinib for further clinical applications. Fostamatinib is designed as a prodrug and cleavage of its active moiety R406 in the intestine. As R406 is the major product in the blood, this review mainly discusses the pharmacokinetics and pharmacodynamics of R406. It is metabolized by cytochrome 3A4 and UGT1A9 in the liver and is dominantly excreted in feces after anaerobic modification by the gut microbiota. As fostamatinib and R406 strongly inhibit the breast cancer resistance protein, the interaction with those substrates, particularly statins, should be carefully monitored. In patients with immune thrombocytopenia, fostamatinib administration started at 100 mg twice daily, and most patients increased to 150 mg twice daily in the clinical trial. Although responders showed a higher R406 concentration than non-responders, the correlation between R406 exposure and achievement of the platelet count as a pharmacodynamic marker was uncertain in the pharmacokinetic/pharmacodynamic analysis. Additionally, R406 concentration was almost halved in patients with a heavy body weight; hence, the exposure-efficacy study for suitable dosing should be continued with post-marketing data. In contrast, the pharmacokinetic/pharmacodynamic analysis for exposure safety revealed that R406 exposure significantly correlated with the incidence of hypertension. Even though the influence of elevated exposure on other toxicities, including diarrhea and neutropenia, is still unclear, careful management is required with dose escalation to avoid toxicity-related discontinuation.

Fostamatinib 是第一个被批准用于治疗慢性免疫性血小板减少症的脾脏酪氨酸激酶抑制剂。本综述总结了福斯塔替尼的临床进展、药代动力学、药效学、药物相互作用、不良事件和综合分析。在整合这些发现的同时，我们讨论了福斯塔替尼的进一步临床应用的培育和改进。 Fostamatinib 被设计为前药，其活性部分 R406 在肠道中裂解。由于R406是血液中的主要产物，本综述主要讨论R406的药代动力学和药效学。它在肝脏中由细胞色素3A4和UGT1A9代谢，经肠道菌群厌氧修饰后主要从粪便中排出。由于福斯塔替尼和 R406 强烈抑制乳腺癌耐药蛋白，因此应仔细监测与这些底物（特别是他汀类药物）的相互作用。在免疫性血小板减少症患者中，福斯塔替尼的给药剂量从 100 mg 每天两次开始，临床试验中大多数患者增加至 150 mg 每天两次。尽管应答者表现出比无应答者更高的 R406 浓度，但在药代动力学/药效分析中，R406 暴露与血小板计数作为药效标记物的实现之间的相关性尚不确定。此外，体重过重的患者中，R406 浓度几乎减半；因此，应根据上市后数据继续进行适当剂量的暴露功效研究。相反，暴露安全性的药代动力学/药效学分析表明，R406暴露与高血压的发生率显着相关。 尽管暴露增加对其他毒性（包括腹泻和中性粒细胞减少症）的影响仍不清楚，但需要谨慎管理剂量递增以避免与毒性相关的停药。