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 ye...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 150μCi[^(14)C]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.展开更多
基金supported by funding from the 13th Five-Year Plan New Drug Creation Program—Isotope Tracer Technology Platform for Clinical Evaluation of Innovative Drugs(Grant No.2017ZX09304032 with project leaders Jun Zhao and Chen Zhou).
文摘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 150μCi[^(14)C]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.
