中国临床药理学杂志2024，Vol.40Issue(14)：2118-2123,6.DOI:10.13699/j.cnki.1001-6821.2024.14.024
[14C]吡罗西尼在中国男性健康受试者体内的药物代谢和排泄研究
Drug metabolism and excretion of[14C]birociclib in Chinese male healthy subjects
庄铨坤 1樊慧蓉 2董世奇 2范宾科 1刘鸣明 3许玲美 3王莉 3刘雪梅 1侯芳1
作者信息
- 1. 北京高博博仁医院Ⅰ期临床研究中心,北京 100071
- 2. 中国医学科学院放射医学研究所放射性药代平台,天津 300110
- 3. 轩竹生物科技股份有限公司,北京 100020
- 折叠
摘要
Abstract
Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.关键词
[14C]吡罗西尼/物质平衡/代谢/药代动力学/同位素Key words
[14 C]birociclib/mass balance/metabolize/pharmacokinetics/isotope分类
医药卫生引用本文复制引用
庄铨坤,樊慧蓉,董世奇,范宾科,刘鸣明,许玲美,王莉,刘雪梅,侯芳..[14C]吡罗西尼在中国男性健康受试者体内的药物代谢和排泄研究[J].中国临床药理学杂志,2024,40(14):2118-2123,6.
