Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults

Abstract

Purpose

Pyrotinib, an irreversible human epidermal growth factor receptor 2 (HER2), is a epidermal growth factor receptor double-target tyrosine kinase inhibitor used for treating HER2-positive breast cancer. This study aimed to evaluate the impact of the strong CYP3A4 inhibitor itraconazole on the safety and pharmacokinetics of pyrotinib in Chinese healthy adults.

Patients and Methods

This was an open-label, randomized, self-control study. Eighteen healthy adults were included in this trial. They received a single 80 mg dose of pyrotinib orally on days 1 and 9, and a 200 mg once-daily dose of itraconazole on days 6 through 22. Blood samples were obtained, and the drug concentration was detected using liquid chromatography/tandem mass spectrometry.

Results

Compared with pyrotinib alone, the exposure to pyrotinib co-administered with itraconazole substantially increased, and the C_max and AUC_0-t increased by 2.78- and 10.8-fold, respectively. No serious adverse events were reported in this trial, and no participant dropped out of the trial because of adverse events.

Conclusion

The exposure to pyrotinib was substantially affected by the action of itraconazole. The concomitant use of pyrotinib with itraconazole might require dose modification of pyrotinib. All treatments were well tolerated in healthy participants.

Clinical Trial Registry

http://www.chinadrugtrials.org.cn/clinicaltrials.prosearch.dhtml, CTR20191866.

Keywords:

• drug–drug interaction
• itraconazole
• pharmacokinetics
• pyrotinib
• safety

Acknowledgments

The authors thank all study participants. This study was sponsored by Jiangsu Hengrui Pharmaceutical Co., Ltd. and supported by the National Major Scientific and Technological Special Project (2020ZX09201014).

Data Sharing Statement

The original data of this study will not be shared due to confidentiality.

Ethical Approval

The study was approved by the ethics committee of The Second Hospital of Anhui Medical University (Hefei, China) and performed according to the ethical principles formulated in the Helsinki Declaration of the World Medical Congress and its amendments.

Informed Consent

All participants included in this study signed informed consent.

Disclosure

The authors are accountable for the content and writing of this manuscript and report no conflicts of interest related to this study.