HSK31858 + itraconazole

HSK31858 + itraconazole is a drug combination utilized in clinical pharmacology studies to evaluate the pharmacokinetic (PK) profile and drug-drug interaction (DDI) potential of HSK31858. HSK31858 is an oral, potent, and highly selective small molecule inhibitor of dipeptidyl peptidase 1 (DPP1), also known as cathepsin C. By inhibiting DPP1, HSK31858 prevents the activation of downstream neutrophil serine proteases (NSPs) such as neutrophil elastase, proteinase 3, and cathepsin G, which are key mediators of inflammation in respiratory diseases like bronchiectasis. Itraconazole, a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, is co-administered in these trials to determine if HSK31858 is a substrate of CYP3A4 and to quantify the impact of metabolic inhibition on its systemic exposure. This combination is specifically studied by Haisco Pharmaceutical Group to inform dosing and safety profiles for HSK31858's clinical development.