Evaluation of drug–drug interactions of a novel potent FLT3 inhibitor SKLB1028 in healthy subjects

• Published in: Clinical and translational science Vol. 17; no. 11; pp. e70063 - n/a
• Main Authors: Chen, Jingcheng, Wu, Jingxuan, Guo, Nini, Song, Yuqin, Li, Lijun, Wang, Bingyan, Li, Jiangshuo, Hou, Mengyu, Yin, Hang, Zhang, Meijuan, Kong, Yanhong, Wu, Xiaofang, Li, Ran, Wu, Le, Gao, Qiannan, Dong, Ruihua
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.11.2024; John Wiley and Sons Inc; Wiley
• Subjects: Acute myeloid leukemia; Adult; Aniline Compounds; Antifungal agents; Area Under Curve; Clinical significance; Cytochrome P-450 CYP2C8 Inhibitors - administration & dosage; Cytochrome P-450 CYP2C8 Inhibitors - pharmacokinetics; Cytochrome P-450 CYP2C8 Inhibitors - pharmacology; Cytochrome P-450 CYP3A Inducers - administration & dosage; Cytochrome P-450 CYP3A Inducers - pharmacology; Cytochrome P-450 CYP3A Inhibitors - administration & dosage; Cytochrome P-450 CYP3A Inhibitors - pharmacokinetics; Cytochrome P-450 CYP3A Inhibitors - pharmacology; Drug dosages; Drug interaction; Drug Interactions; Drug metabolism; Drug therapy; Electrocardiography; Enzymes; fms-Like Tyrosine Kinase 3 - antagonists & inhibitors; fms-Like Tyrosine Kinase 3 - metabolism; Gemfibrozil; Gemfibrozil - administration & dosage; Gemfibrozil - pharmacokinetics; Gemfibrozil - pharmacology; Healthy Volunteers; Humans; Itraconazole; Itraconazole - administration & dosage; Itraconazole - pharmacokinetics; Itraconazole - pharmacology; Kinases; Leukemia; Male; Medical prognosis; Mutation; Pharmacokinetics; Prescription drugs; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - pharmacology; Protein turnover; Pyrazines - administration & dosage; Pyrazines - pharmacokinetics; Pyrazines - pharmacology; Rifampin; Rifampin - administration & dosage; Rifampin - pharmacokinetics; Rifampin - pharmacology; Sample size; Software; Vital signs; Young Adult

SKLB1028 is a novel multi‐target protein kinase inhibitor under investigation for the treatment of FLT3‐ITD mutated acute myeloid leukemia. Based on the preclinical characterization of SKLB1028 metabolism, three drug–drug interaction clinical studies were performed to investigate the effects of itra...