Effect of Fluconazole on the Pharmacokinetics of Pyrotinib Maleate: A Single-Center, Open, Single-Dose, Self-Controlled Study in Healthy Chinese Participants

What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor (EGFR) human 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes its metabolism influenced apparently by CYP3A4 strong inhibitor, but effect of moderate still unclear a enzyme. This study evaluated fluconazole, widespread antifungal medication, on pharmacokinetics safety tolerance pyrotinib. Methods. was open, single-dose, self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All administered fluconazole days 6–18 pyrotinib 1 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under concentration–time curve from 0 last measurable (AUC0−t), extrapolated infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume distribution (Vz/F), clearance (CL/F) calculated using WinNonlin software (version 8.1). Safety assessed throughout process. Results Discussion. Compared with single administration exposure level enhanced significantly after coadministration fluconazole. geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) Cmax, AUC0−t, AUC0−∞ 2.16, 3.6, 3.5, respectively. parameter t1/2 14.16 h 24.03 h, CL/F 275.06 L/h 78.42 L/h, for alone No serious adverse events reported trial, no participant withdrew trial because events. New Conclusion. PK profile substrate, increased levels prolonged t1/2. Dosage adjustment suggested application when coadministered or other inhibitors/inducers.