AUTHOR=Zhang Hua , Yan Shu , Zhan Yan , Ma Sheng , Bian Yicong , Li Shaorong , Tian Junjun , Li Guangze , Zhong Dafang , Diao Xingxing , Miao Liyan 

TITLE=A mass balance study of [14C]SHR6390 (dalpiciclib), a selective and potent CDK4/6 inhibitor in humans

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1116073

DOI=10.3389/fphar.2023.1116073

ISSN=1663-9812

ABSTRACT=<p>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 [<sup>14</sup>C]SHR6390 (150 µCi) in this research. The <italic>Tmax</italic> of SHR6390 was 3.00 h. In plasma, the <italic>t</italic><sub>1/2</sub> of SHR6390 and its relative components was approximately 17.50 h. The radioactivity B/P (blood-to-plasma) AUC<sub>0-t</sub> 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<sub>0-24 h</sub> 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.</p>