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

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

doi:10.3389/fphar.2023.1116073

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

Front Pharmacol. 2023 Mar 31:14:1116073. doi: 10.3389/fphar.2023.1116073. eCollection 2023.

Authors

Hua Zhang^{1

2}, Shu Yan³, Yan Zhan³, Sheng Ma^{1

2}, Yicong Bian^{1

2}, Shaorong Li⁴, Junjun Tian³, Guangze Li⁴, Dafang Zhong³, Xingxing Diao³, Liyan Miao^{1

2}

Affiliations

¹ Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, China.
³ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
⁴ Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, Jiangsu, China.

Abstract

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 [¹⁴C]SHR6390 (150 µCi) in this research. The Tmax of SHR6390 was 3.00 h. In plasma, the t _1/2 of SHR6390 and its relative components was approximately 17.50 h. The radioactivity B/P (blood-to-plasma) AUC_0-t 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_{0-24 h} 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.

Keywords: CDK; SHR6390; [14C]SHR6390; drug metabolism; pharmacokinetics; radioactivity.

Grants and funding

This study was funded by Jiangsu Hengrui Pharmaceutical Co., Ltd. (Limited Company), and part of the funding was from the National Natural Science Foundation of China (81903701). This work was also supported by the national key new drug creation project (2017ZX09304-021), Suzhou Key Laboratory of Clinical Research and Personalized Medicine (SZS201719) and the special research fund of Wu Jieping Medical Foundation of Clinical Pharmacy Branch of Chinese Medical Association (320.6750.19090-50).