Zhang Hua, Yan Shu, Zhan Yan, Ma Sheng, Bian Yicong, Li Shaorong, Tian Junjun, Li Guangze, Zhong Dafang, Diao Xingxing, Miao Liyan
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, China.
Front Pharmacol. 2023 Mar 31;14:1116073. doi: 10.3389/fphar.2023.1116073. eCollection 2023.
SHR6390 (dalpiciclib) is a selective and effective cyclin-dependent kinase (CDK) 4/6 inhibitor and an effective cancer therapeutic agent. On 31 December 2021, the new drug application was approved by National Medical Product Administration (NMPA). The metabolism, mass balance, and pharmacokinetics of SHR6390 in 6 healthy Chinese male subjects after a single oral dose of 150 mg [C]SHR6390 (150 µCi) in this research. The of SHR6390 was 3.00 h. In plasma, the of SHR6390 and its relative components was approximately 17.50 h. The radioactivity B/P (blood-to-plasma) AUC ratio was 1.81, indicating the preferential distribution of drug-related substances in blood cells. At 312 h after administration, the average cumulative excretion of radioactivity was 94.63% of the dose, including 22.69% in urine and 71.93% in stool. Thirteen metabolites were identified. In plasma, because of the low level of radioactivity, only SHR6390 was detected in pooled AUC plasma. Stool SHR6390 was the main component in urine and stool. Five metabolites were identified in urine, and 12 metabolites were identified in stool. Overall, faecal clearance is the main method of excretion.
SHR6390（达尔西利）是一种选择性且有效的细胞周期蛋白依赖性激酶（CDK）4/6抑制剂，也是一种有效的癌症治疗药物。2021年12月31日，该新药申请获得国家药品监督管理局（NMPA）批准。本研究中，6名健康中国男性受试者单次口服150mg [C]SHR6390（150µCi）后，对SHR6390的代谢、质量平衡和药代动力学进行了研究。SHR6390的半衰期为3.00小时。在血浆中，SHR6390及其相关成分的半衰期约为17.50小时。放射性B/P（血药浓度与血浆浓度）AUC比值为1.81，表明药物相关物质在血细胞中优先分布。给药后312小时，放射性的平均累积排泄量为给药剂量的94.63%，其中尿液中排泄22.69%，粪便中排泄71.93%。共鉴定出13种代谢物。在血浆中，由于放射性水平较低，在合并的AUC血浆中仅检测到SHR6390。粪便中的SHR6390是尿液和粪便中的主要成分。尿液中鉴定出5种代谢物，粪便中鉴定出12种代谢物。总体而言，粪便清除是主要的排泄途径。
