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

Supplementary Material 1

Supplemental material, sj-pdf-1-imr-10.1177_03000605221126382 for Misplaced drainage tube inserted in the vein in a percutaneous nephrostomy: a case series by Yuanming Song, Changyong Zhao, Zhongyi Zhang, Shun Zhan, Zuze Qiu and Daobing Li in Journal of International Medical Research

Supplemental material, sj-pdf-2-imr-10.1177_03000605221126382 for Misplaced drainage tube inserted in the vein in a percutaneous nephrostomy: a case series by Yuanming Song, Changyong Zhao, Zhongyi Zhang, Shun Zhan, Zuze Qiu and Daobing Li in Journal of International Medical Research