Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans
文献类型：期刊论文
| 作者 | Liu, Donghui5,6; Li, Qian3,4; Yan, Shu5; Zhang, Xinyue5,6; Li, Weiqiang5; Wang, Feiyu5,6; Gao, Lei5; Geng, Fei5; Zhou, Haiyan3,4; Ye, Panpan3,4 |
| 刊名 | CANCER CHEMOTHERAPY AND PHARMACOLOGY
 |
| 出版日期 | 2025-12-01 |
| 卷号 | 95期号:1页码:14 |
| 关键词 | PLB1004 [C-14]PLB1004 Radioactivity Mass balance EGFR-TKI |
| ISSN号 | 0344-5704 |
| DOI | 10.1007/s00280-024-04744-7 |
| 通讯作者 | Diao, Xingxing(xxdiao@simm.ac.cn) ; Zhao, Wei(zhao4wei2@hotmail.com) |
| 英文摘要 | Purpose PLB1004, developed by Beijing Avistone Biotechnology Co., Ltd., is a safe, highly selective, and efficient irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) employed in treating non-small-cell-lung-cancer (NSCLC). This study investigated its pharmacokinetics, mass balance, and metabolism in 6 healthy Chinese male subjects treated with 160 mg (70 mu Ci) [C-14]PLB1004. Methods Following drug administration, samples of blood, urine and feces were collected for quantitative determination of total radioactivity and metabolites were identified through radioactivity detection coupled with UHPLC-MS/MS. Results Following drug administration, the median radioactive T(max )was 4.17 h in plasma, with the average t(1/2) of PLB1004-related components in plasma of approximately 54.3 h. Over 264 h post-administration, the average cumulative excretion among the six subjects was 95.01% of the administered dose, with 84.71% and 10.30% excreted in feces and urine, respectively. Nine metabolites were characterized and identified and the parent drug PLB1004 was detected in plasma, urine, and feces. Among these metabolites, M689 was the most prevalent one in plasma, urine, and feces, constituting 25.37% of the total plasma radioactivity, and 55.88% and 1.73% of the administrated dose in feces and urine, respectively. Conclusion Fecal excretion emerged as PLB1004 excretion route, while urinary excretion via the kidneys served as the secondary route. The primarily metabolic pathways are oxidation, demethylation, dehydrogenation, and cysteine conjugation in humans. |
| WOS关键词 | CELL LUNG-CANCER ; FACTOR RECEPTOR EGFR ; GLUTATHIONE ; PLASMA |
| 资助项目 | National Natural Science Foundation of China ; Beijing Avistone Biotechnology Co., Ltd. ; Key Technologies R&D Program of Guangdong Province[2023B1111030004] ; National Key R&D Program of China[2022YFF1202600] ; [82373938] ; [82104276] ; [82204585] |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001392909000001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315606]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Diao, Xingxing; Zhao, Wei |
| 作者单位 | 1.XenoFinder Co Ltd, Suzhou 215123, Peoples R China 2.Beijing Avistone Biotechnol Co Ltd, Beijing 100102, Peoples R China 3.Shandong Prov Qianfoshan Hosp, Shandong Engn & Technol Res Ctr Pediat Drug Dev, Shandong Med & Hlth Key Lab Clin Pharm, Jinan 250014, Peoples R China 4.Shandong First Med Univ, Dept Clin Pharm, Affiliated Hosp 1, Jinan 250014, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Ctr Drug Metab & Pharmacokinet, Shanghai 201210, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Donghui,Li, Qian,Yan, Shu,et al. Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2025,95(1):14. |
| APA | Liu, Donghui.,Li, Qian.,Yan, Shu.,Zhang, Xinyue.,Li, Weiqiang.,...&Zhao, Wei.(2025).Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans.CANCER CHEMOTHERAPY AND PHARMACOLOGY,95(1),14. |
| MLA | Liu, Donghui,et al."Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans".CANCER CHEMOTHERAPY AND PHARMACOLOGY 95.1(2025):14. |
入库方式： OAI收割
来源：上海药物研究所
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