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

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...

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Autores principales: Liu, Yueyue, Zhang, Qian, Lu, Chao, Hu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203185/
https://www.ncbi.nlm.nih.gov/pubmed/34140765
http://dx.doi.org/10.2147/DDDT.S312310
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author Liu, Yueyue
Zhang, Qian
Lu, Chao
Hu, Wei
author_facet Liu, Yueyue
Zhang, Qian
Lu, Chao
Hu, Wei
author_sort Liu, Yueyue
collection PubMed
description 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.
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spelling pubmed-82031852021-06-16 Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults Liu, Yueyue Zhang, Qian Lu, Chao Hu, Wei Drug Des Devel Ther Original Research 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. Dove 2021-06-10 /pmc/articles/PMC8203185/ /pubmed/34140765 http://dx.doi.org/10.2147/DDDT.S312310 Text en © 2021 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Yueyue
Zhang, Qian
Lu, Chao
Hu, Wei
Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title_full Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title_fullStr Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title_full_unstemmed Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title_short Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults
title_sort multiple administrations of itraconazole increase plasma exposure to pyrotinib in chinese healthy adults
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203185/
https://www.ncbi.nlm.nih.gov/pubmed/34140765
http://dx.doi.org/10.2147/DDDT.S312310
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