Drug-drug interaction study between SHC014748M and itraconazole and rifampicin

Objective To evaluate the pharmacokinetics of SHC014748M under the influence of different drugs . SHC014748M, a selective PI3Kδ inhibitor, has shown potential therapeutic value in patients with CLL/SLL and NHL in clinical studies. Methods This study employed a single-center, two-period, open-label, sequential-dose design. Key pharmacokinetic parameters were calculated using non-compartmental analysis using WinNonlin software (version 8.2). Results Coadministration of SHC014748M with CYP3A4/5 inhibitors or inducers significantly affected the maximum plasma concentration (C _max ) , the area under the curve at the cutoff time point (AUC _0-t ), and the area under the curve extending to infinity (AUC _0-∞ ). This drug-drug interaction demonstrated statistically significant differences in pharmacokinetic parameters (90% confidence interval for the geometric mean ratio outside the 80.00% to 125.00% equivalence range). Conclusions Since SHC014748M is a substrate of CYP3A4/5 metabolizers, it may cause drug-drug interactions with CYP3A4/5 inhibitors and inducers during clinical use. In this study, SHC014748M capsules showed good tolerability. Trial registration Registration authority: China Drug Trials, TRN:CTR20201782, Registration date: August 27, 2020.