Pharmacokinetics,mass balance,and metabolism of 14C TPN171,a novel PDE5 inhibitor,in humans for the treatment of pulmonary arterial hypertension
文献类型：期刊论文
| 作者 | He Yifei3; Liu Yin3; Yu Jinghua3; Cheng Huan3; Odilov Abdullajon3; Yang Feipu3; Tian Guanghui2; Yao Xiumei2; Duan Huaqing2; Yu Chengyin1 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2023 |
| 卷号 | 44期号:1页码:221 |
| 关键词 | TPN171 14CTPN171 PDE5 inhibitor pulmonary arterial hypertension healthy volunteers pharmacokinetics metabolite identification mass balance |
| ISSN号 | 1671-4083 |
| 英文摘要 | TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED),which currently is undergoing phase II clinical trials in China.In this single-center,single-dose,nonrandomized,and open design study,radiolabeled 14CTPN171 was used to investigate the metabolic mechanism,pharmacokinetic characteristics,and clearance pathways of TPN171 in 6 healthy Chinese male volunteers.Each volunteer was administered a single oral suspension of 10 mg (100 μCi) of 14CTPN171.We found that TPN171 was absorbed rapidly in humans with a peak time (T_(max)) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma.Excretion of radiopharmaceutical-related components was collected 216 h after administration,accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces).TPN171 underwent extensive metabolism in humans.Twenty-two metabolites were detected in human plasma,urine,and feces using a radioactive detector combined with a high-resolution mass spectrometer.According to radiochromatograms,a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma.However,according to the Food and Drug Administration (FDA) guidelines,no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite,but the compound is still worthy of attention.The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation),dehydrogenation,N-dealkylation,O-dealkylation,amide hydrolysis,glucuronidation,and acetylation.Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites,and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent.According to the incubation data,M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9),followed by UGT1A7 and UGT1A10. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304845]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.Shanghai Xuhui Central Hospital 2.Vigonvita Life Sciences Co.,Ltd 3.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | He Yifei,Liu Yin,Yu Jinghua,et al. Pharmacokinetics,mass balance,and metabolism of 14C TPN171,a novel PDE5 inhibitor,in humans for the treatment of pulmonary arterial hypertension[J]. ACTA PHARMACOLOGICA SINICA,2023,44(1):221. |
| APA | He Yifei.,Liu Yin.,Yu Jinghua.,Cheng Huan.,Odilov Abdullajon.,...&Diao Xingxing.(2023).Pharmacokinetics,mass balance,and metabolism of 14C TPN171,a novel PDE5 inhibitor,in humans for the treatment of pulmonary arterial hypertension.ACTA PHARMACOLOGICA SINICA,44(1),221. |
| MLA | He Yifei,et al."Pharmacokinetics,mass balance,and metabolism of 14C TPN171,a novel PDE5 inhibitor,in humans for the treatment of pulmonary arterial hypertension".ACTA PHARMACOLOGICA SINICA 44.1(2023):221. |
入库方式： OAI收割
来源：上海药物研究所
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