Effect of itraconazole on the safety and pharmacokinetics of antitumor SHR6390

The experimental drug SHR6390 has anti-tumor activity as a cyclin dependent kinase 4/6 inhibitor and is metabolized primarily by the cytochrome P450 3A4 enzyme. Therefore, purpose of this trial was to evaluate safety pharmacokinetics SHR6390, potent inhibitor, in healthy Chinese subjects. In study, 18 subjects received single oral dose 50 mg on day 1, multiple doses 200 itraconazole days 12–24 for 13 days, 15. After coadministration with itraconazole, maximum plasma concentration (Cmax) increased 70.7% (from 14.3 ng/ml 24.5 ng/ml), area under time curve from 0 T (AUC0-T) 110.8% 468 h∙ng/mL 988 h∙ng/mL. concentration-time extrapolated ∞(AUC0-∞) increases 509 H∙ng/mL 1,040 h∙ng/mL, an increase 105.1%. Oral gap (CL/F) decreased (47.9 L/h 98.3 L/h) apparent volume distribution (Vz/F) (4190 L 5890 L). According common terminology criteria, 15 32 adverse events were reported (AEs) (27 SHR6390-related AEs Itraconazole-related AEs), all Class 1 events. Overall, co-administration Itraconazole exposure Both alone showed acceptable profiles, which warrants further investigation. SHR-6390 clinical been applied registration, classified Chemical drugs 1. study registration number:ClinicalTrials.gov Identifier: NCT04423601 ( https://clinicaltrials.gov/ )