Publication: Cancer Medicine
Abstract
SHR2554 is a novel oral EZH2 inhibitor with broad-spectrum anti-tumor activity that is primarily metabolized by CYP3A4, raising concern about interactions with strong CYP3A4 inhibitors. This open-label Phase I study in 18 healthy Chinese subjects evaluated the pharmacokinetic interaction between SHR2554 and itraconazole (a strong CYP3A4 inhibitor), with plasma concentrations measured by HPLC-MS/MS and pharmacokinetic parameters calculated using Phoenix WinNonlin. Co-administration with itraconazole increased SHR2554 Cmax, AUC0-t, and AUC0-inf by 7.73-, 12.47-, and 23.75-fold, respectively, though the combination was well tolerated with a good safety profile. The findings indicate a substantial pharmacokinetic interaction between SHR2554 and itraconazole, information important for guiding co-administration decisions in future clinical use.
Author(s): Deng K, Zou Y, Zou C, Wang H, Xiang Y, Yang X, Yang S, Cui C, Yang G, Huang J
Published: July 16, 2022
Phoenix WinNonlin: Quantifying a Major Drug Interaction
Phoenix WinNonlin's pharmacokinetic analysis captured up to a 24-fold exposure increase in this drug interaction study between an investigational EZH2 inhibitor and itraconazole. As part of a Phoenix platform relied on by more than 11,000 users worldwide, Phoenix WinNonlin can be paired with AI PK Reports to turn an analysis into a complete PK document in minutes rather than days.
