Effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in vivo.

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2024-12-10 DOI:10.1016/j.jchromb.2024.124425

Zhi Wang, Zefang Yu, Lingzhi Fang, Jing An, Chaojun Xue, Xin Zhou, Xiao Li, Ying Li, Zhanjun Dong

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Abstract

Furmonertinib, a third generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is used for non-small cell lung cancer (NSCLC). Rivaroxaban and apixaban are direct oral anticoagulants (DOACs) used for venous thromboembolism (VTE), which is a frequent comorbid with NSCLC. They are substrates of CYP3A4, P-gp and BCRP, whereas furmonertinib is an inhibitor of P-gp and BCRP. This study aimed to disclose the extent of effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban. Rats were divided into four groups (n = 6) that received rivaroxaban (group 1), furmonertinib and rivaroxaban (group 2), apixaban (group 3), furmonertinib and apixaban (group 4). The concentrations of drugs were measured by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Furmonertinib increased the C_max and AUC_0-t of rivaroxaban by 1.66 and 2.07-fold, whereas decreased the CL_z/F by 1.70-fold and V_z/F 1.27-fold. Furthermore, furmonertinib caused similar changes in apixaban pharmacokinetics. The pharmacokinetic results suggest that it is essential to alert the effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in clinical practice.

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氟莫尼替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs），用于治疗非小细胞肺癌（NSCLC）。利伐沙班和阿哌沙班是直接口服抗凝剂（DOACs），用于治疗静脉血栓栓塞症（VTE），VTE是NSCLC的常见合并症。它们是CYP3A4、P-gp和BCRP的底物，而福莫尼替尼是P-gp和BCRP的抑制剂。本研究旨在揭示呋莫尼替尼对利伐沙班或阿哌沙班药代动力学的影响程度。大鼠分为四组（n = 6），分别接受利伐沙班（第1组）、呋莫尼替尼和利伐沙班（第2组）、阿哌沙班（第3组）、呋莫尼替尼和阿哌沙班（第4组）治疗。药物浓度通过超高效液相色谱-串联质谱法（UPLC-MS/MS）测定。呋莫尼替尼使利伐沙班的Cmax和AUC0-t分别增加了1.66倍和2.07倍，CLz/F降低了1.70倍，Vz/F降低了1.27倍。此外，呋莫尼替尼也使阿哌沙班的药代动力学发生了类似的变化。药代动力学结果表明，在临床实践中必须警惕呋莫尼替尼对利伐沙班或阿哌沙班药代动力学的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.