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Cancer Chemotherapy and Pharmacology

Erschienen in:

11.05.2023 | Clinical Trial Report

Itraconazole interferes in the pharmacokinetics of fuzuloparib in healthy volunteers

verfasst von: Chaoying Hu, Yanping Zhang, Tong Pei, Ping Liu, Lan Zhang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2023

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Abstract

Objective

Fuzuloparib is an orally administered poly [ADP-ribose] polymerase 1 (PARP1) inhibitor and has potential anti-tumor effect on ovarian cancer (such as fallopian tube cancer and primary peritoneal cancer) in China. As fuzuloparib is metabolized mainly by CYP3A4, we explored the effect of itraconazole, a strong CYP3A4 inhibitor, on a single oral dose of fuzuloparib in healthy male subjects.

Methods

An open-label, single-arm, fixed sequence study was conducted. Twenty healthy adult males received one single dose of fuzuloparib (20 mg) with one dose administered alone and the other dose coadministered with itraconazole. Subjects received 200 mg QD itraconazole for 6 days during the study. Serials of blood samples were collected pre-dose of each fuzuloparib capsule administration and 48 h post-dose, and were used to analyze the PK parameters of fuzuloparib.

Results

Coadministration of repeated 200 mg QD oral doses of itraconazole for 6 days increased fuzuloparib exposure by 1.51-fold and 4.81-fold for peak plasma concentration and area under the plasma concentration–time curve (AUC), respectively. Oral administration of 20 mg fuzuloparib alone or together with itraconazole was safe and tolerable in healthy male subjects.

Conclusion

The CYP3A4 inhibitor itraconazole has a significant influence on the PK behavior of fuzuloparib, suggesting to avoid using strong CYP3A4 inhibitors simultaneously with fuzuloparib. If it is necessary to use a strong CYP3A4 inhibitor, fuzuloparib would be discontinued and be restored to the original dose and frequency of administration after 5–7 half lives of CYP3A4 inhibitor stopped.

Trial registration

http://www.chinadrugtrials.org.cn/index.html, CTR20191271.

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Titel: Itraconazole interferes in the pharmacokinetics of fuzuloparib in healthy volunteers
verfasst von: Chaoying Hu
Yanping Zhang
Tong Pei
Ping Liu
Lan Zhang
Publikationsdatum: 11.05.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2023
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-023-04536-5

Springer Medizin

Itraconazole interferes in the pharmacokinetics of fuzuloparib in healthy volunteers

Abstract

Objective

Methods

Results

Conclusion

Trial registration

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Update Onkologie

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Trial registration

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