Absorption, metabolism, excretion, and safety of [14C]almonertinib in healthy Chinese subjects

作者：Chen Zhou, Lijun Xie, Wei Liu, Lingling Zhang, Sufeng Zhou, Lu Wang, Juan Chen, Huan Li, Yuqing Zhao, Bei Zhu, Sijia Ding, Chen Zhang, Feng Shao · 发表于：Annals of Translational Medicine · 年份：2021 · DOI：10.21037/atm-21-1606 · 被引用次数：20 · 研究领域：Lung Cancer Treatments and Mutations、Fibroblast Growth Factor Research、Cytokine Signaling Pathways and Interactions

Background: Almonertinib Mesilate Tablets (HS-10296, Hansoh Pharma, Shanghai, China) is a novel and selective third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). A phase I study of almonertinib in patients with non-small cell lung cancer (NSCLC) demonstrated a linear metabolic trend, a good tolerability/safety profile, and preliminary antitumor activity. However, the metabolism, excretion, and substance balance of almonertinib has not been clearly determined. Here, we investigated the pharmacokinetic characteristics and safety profile of almonertinib following a single oral dose (110 mg/50 µCi) in healthy Chinese male participants.Methods: Total radioactivity (TRA) in whole blood, plasma, urine, and feces was measured by utilizing a liquid scintillation counter to obtain almonertinib substance balance data. The pharmacokinetic parameters of [14C]almonertinib and the parent drug almonertinib in whole blood and plasma were analyzed with noncompartmental analysis in the WinNonlin software (Pharsight Corp). The major metabolites in plasma, urine, and feces were analyzed by high-performance liquid chromatography (HPLC) coupled with an online or offline isotope detector. The safety of the drug was evaluated after administration.Results: The safety and tolerability of a single oral dose of 110 mg/50 µCi [14C] almonertinib suspension were good in healthy Chinese male participants. There was no significant abnormality or special adverse reaction. TR...