Study of the mass balance,biotransformation,and safety of[14C]IBI351 in healthy Chinese subjects
Shuaishuai Wang1
Wen Lin1
Bilal Ahmed1
Tianqi Zhong2
Jun Zhao2
Lijun Xie2
Hao Feng3
Juan Chen2
Chen Zhang4
Peng Yan4
Shirui Zheng5
Lingge Cheng5
Yipeng Cheng5
Bei Zhu2
Feng Han1
Lulu Zhang1
Chen Zhou2
1.Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases,Ministry of Education,International Joint Laboratory for Drug Target of Critical Illnesses,Key Laboratory of Cardiovascular and Cerebrovascular Medicine,School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Phase Ⅰ Clinical Trial Unit,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China3.Value Pharmaceutical Services Co.,Ltd.,Nanjing,Jiangsu 211806,China4.Nuclear Medicine Department,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China5.Innovent Biologics Co.,Ltd.,Shanghai 201107,China
摘要：IBI351,a synthetic compound,exerts its anti-tumor effects by specifically,covalently,and irreversibly modifying the 12th cysteine residue of KRAS G12C.However,the pharmacokinetic profile of IBI351 in humans has not yet been reported.The current study aimed to investigate the pharmacokinetics and safety of IBI351 in healthy Chinese male subjects.A single oral dose of 600 mg combined with 150 μCi[14C]IBI351 was administered to six healthy male volunteers.Blood,urine,and fecal samples were collected at multiple time points to quantify the parent drug and its metabolites.IBI351 showed favorable pharmacokinetic characteristics and was well tolerated by all participants.Seventeen major metabolites were identified in plasma,urine,and feces.The main metabolic pathways included oxidation,hydrogenation,sulfonate conjugation,glucuronide conjugation,and cysteine conjugation.Excretion of IBI351 and its metabolites occurred mainly through feces.Collectively,this first-in-human study provides essential data on the metabolism and safety of IBI351 in Chinese subjects and lays the foundation for its further clinical development as a novel anti-tumor drug.
机标关键词：chinesebalancestudysafetymassbiotransformhealthysubjects
分类号：R965(药理学)
论文发表日期：2025-07-30
在线出版日期：2025-10-11（本平台首次上网日期，不代表文献的发表时间）
页数：12( 382-393 )
英文信息