Abstract：
This open-label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug-drug interaction between rilzabrutinib and quinidine (an inhibitor of P-glycoprotein [P-gp] and CYP2D6) or rifampin (an inducer of CYP3A and P-gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash-out period, after co-administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing). Quinidine had no significant effect on rilzabrutinib pharmacokinetics. Rifampin decreased rilzabrutinib exposure (the geometric mean of Cmax and AUC0-∞ decreased by 80.5% and 79.5%, respectively). Single oral doses of rilzabrutinib, with or without quinidine or rifampin, appeared to be well tolerated. These findings indicate that rilzabrutinib is a substrate for CYP3A but not a substrate for P-gp.
摘要：
这个开放标签，我们对健康成年参与者进行了1期研究,以评估利扎布替尼与奎尼丁(P-糖蛋白[P-gp]和CYP2D6的抑制剂)或利福平(CYP3A和P-gp的诱导剂)之间的潜在药物-药物相互作用.在第1天和第1天再次口服400mg利扎布替尼的单次口服剂量后，测量利扎布替尼的血浆浓度，在经历了一段时间后，利扎布替尼和奎尼丁或利福平共同给药后。具体来说,从第7天至第11天(N=16),每8小时一次给予奎尼丁300mg,共5天;从第7天至第17天(N=16),利福平每天一次给予600mg,共11天,利扎布替尼在第10天上午(奎尼丁给药期间)或第16天(利福平给药期间)给予.奎尼丁对rilzabrutinib药代动力学无显著影响。利福平降低了rilzabrutinib的暴露（Cmax和AUC0-∞的几何平均值分别降低了80.5%和79.5%，分别)。单一口服剂量的里扎布替尼，有或没有奎尼丁或利福平，似乎很宽容。这些发现表明里扎布替尼是CYP3A的底物，但不是P-gp的底物。
