Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects
文献类型：期刊论文
| 作者 | Ma, Sheng3,4; Wang, Xin2; Yan, Shu1; Miao, Liyan3,4; Wan, Xiaojing2; Ding, Dawei2; Yu, Ding2; Diao, Xingxing1; Wang, Xunqiang2; Zhang, Hua3,4 |
| 刊名 | CANCER CHEMOTHERAPY AND PHARMACOLOGY
 |
| 出版日期 | 2024-03-20 |
| 页码 | 11 |
| 关键词 | Envonalkib TQ-B3139 Pharmacokinetics Mass balance Excretion Metabolism |
| ISSN号 | 0344-5704 |
| DOI | 10.1007/s00280-024-04647-7 |
| 通讯作者 | Wang, Xunqiang(wxq@cttq.com) ; Zhang, Hua(zhanghua_suzhou@163.com) |
| 英文摘要 | Purpose Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of C-14-radiolabeled envonalkib in healthy Chinese male subjects. Methods A single oral dose of 600 mg (150 mu Ci) [C-14]envonalkib was administered to healthy male subjects under fasted state. Samples of blood, urine and feces were collected for quantitative determination of total radioactivity and unchanged envonalkib, and the metabolites identification. Results After dosing, the median T-max of radioactivity was 4 h and the mean t(1/2) was 65.2 h in plasma. The exposure of total radioactivity was much higher than that of unchanged envonalkib in plasma. The mean total recovery of the radiolabeled dose was 93.93% over 504 h post-dose, with 15.23% in urine and 78.71% in feces. Envonalkib underwent extensive metabolism and a total of 15 metabolites were identified in plasma, urine, and feces. Unchanged envonalkib and its major metabolite M315 were the main components in plasma, accounting for 20.37% and 33.33% of total plasma radioactivity. In urine, O-dealkylation metabolite M315 was the major component accounted for 7.98% of dose. In feces, 16.01% of dose was excreted as cysteine conjugate M434-1. Envonalkib was well tolerated and there were no serious adverse events observed in the study. Conclusion Envonalkib was extensively metabolized prior to excretion and eliminated primarily as metabolites via feces. |
| WOS关键词 | LUNG-CANCER ; CRIZOTINIB ; EXCRETION |
| 资助项目 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001190121400001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310360]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Xunqiang; Zhang, Hua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Chia Tai Tianqing Pharmaceut Grp Co Ltd, Dept Clin Res Ctr, Nanjing, Peoples R China 3.Soochow Univ, Inst Interdisciplinary Drug Res & Translat Sci, Coll Pharmaceut Sci, Suzhou, Peoples R China 4.Soochow Univ, Affiliated Hosp 1, Dept Pharm, Suzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Sheng,Wang, Xin,Yan, Shu,et al. Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2024:11. |
| APA | Ma, Sheng.,Wang, Xin.,Yan, Shu.,Miao, Liyan.,Wan, Xiaojing.,...&Zhang, Hua.(2024).Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects.CANCER CHEMOTHERAPY AND PHARMACOLOGY,11. |
| MLA | Ma, Sheng,et al."Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects".CANCER CHEMOTHERAPY AND PHARMACOLOGY (2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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