Absorption, distribution, metabolism, and excretion of [C-14]TPN729 after oral administration to rats
文献类型：期刊论文
| 作者 | Cheng, Huan2,3; Yu, Jinghua2; Yang, Chen2; Zhang, Ning2; Fan, Zhen1; Zhang, Xiaojuan1; Wang, Junchen1; Wang, Zhen2 ; Zhong, Da-Fang2; He, Ji-Xiang3
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| 刊名 | XENOBIOTICA
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| 出版日期 | 2022-01-27 |
| 页码 | 12 |
| 关键词 | TPN729 [C-14]TPN729 mass balance tissue distribution metabolism |
| ISSN号 | 0049-8254 |
| DOI | 10.1080/00498254.2022.2030504 |
| 通讯作者 | He, Ji-Xiang(987850250@qq.com) ; Yan, Shu(yanshu@simm.ac.cn) ; Diao, Xingxing(xxdiao@simm.ac.cn) |
| 英文摘要 | TPN729, a novel phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), is in phase II clinical trials in China. Previous studies suggested that TPN729 possesses promising therapeutic value. In previous non-radiolabeled rat excretion studies, the recovery of TPN729 and its major metabolites accounted for approximately 8.58% of the administration dose in urine and faeces by 48 h post-dose. To solve this problem and further study the metabolism of TPN729 in rats, we used the radio-isotopic tracing technique for the first time. In this study, the mass balance, tissue distribution, and metabolism of TPN729 were evaluated in rats after a single oral dose of 25 mg/kg [C-14]TPN729 (150 mu Ci/kg). At 168 h post-dose, the mean total radioactivity recovery of the dose was 92.13%. Faeces was the major excretion route, accounting for 74.63% of the dose, and urine excretion accounted for 17.50%. After oral administration of [C-14]TPN729, radioactivity was widely distributed in all examined tissues, and a higher radioactivity concentration was observed in the stomach, large intestine, lung, liver, small intestine, and eyes. The concentration of drug-related materials were similar in plasma and blood cells. A total of 51 metabolites were identified in rat plasma, urine, faeces, and bile, and the predominant metabolically susceptible position of TPN729 was the pyrrolidine moiety. The main metabolic pathways were N-dealkylation, oxidation, and dehydrogenation. In summary, we solved the previous problem of low drug recovery, elucidated the major excretion pathway, determined the tissue distribution patterns, and investigated the metabolism of TPN729 in rats by using a radioisotopic tracing technique. |
| WOS关键词 | ERECTILE DYSFUNCTION ; DRUG-METABOLISM ; IDENTIFICATION ; PHARMACOKINETICS ; INHIBITORS ; AVANAFIL |
| 资助项目 | National Natural Science Foundation of China[81903701] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000747556800001 |
| 出版者 | TAYLOR & FRANCIS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300501]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | He, Ji-Xiang; Yan, Shu; Diao, Xingxing |
| 作者单位 | 1.Henan Topfond Pharma Co Ltd, Zhumadian, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Shandong Univ Tradit Chinese Med, Sch Pharmaceut Sci, Jinan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Huan,Yu, Jinghua,Yang, Chen,et al. Absorption, distribution, metabolism, and excretion of [C-14]TPN729 after oral administration to rats[J]. XENOBIOTICA,2022:12. |
| APA | Cheng, Huan.,Yu, Jinghua.,Yang, Chen.,Zhang, Ning.,Fan, Zhen.,...&Diao, Xingxing.(2022).Absorption, distribution, metabolism, and excretion of [C-14]TPN729 after oral administration to rats.XENOBIOTICA,12. |
| MLA | Cheng, Huan,et al."Absorption, distribution, metabolism, and excretion of [C-14]TPN729 after oral administration to rats".XENOBIOTICA (2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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