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- Title
Effect of fluconazole on the pharmacokinetics of fuzuloparib: an open-label, crossover study in Chinese healthy male volunteers.
- Authors
Chen, Xue; Yang, Feng; Zhao, Jiao; Tang, Qi; Heng, Jianfu; Deng, Jun; Zhang, Jin; Chen, Yong; Li, Kunyan; Wang, Jing
- Abstract
Purpose: Fuzuloparib (AiRuiYiTM, formerly fluzoparib, SHR3162) is a new orally active poly adenosine diphosphate ribose polymerase (PARP) inhibitor. It has multiple pharmacological activities in breast, ovarian, and prostatic cancer. Fuzuloparib is mainly metabolized through the enzyme CYP3A4 may slow fuzuloparib metabolism and increase its concentrations in blood. We evaluated the pharmacokinetics and tolerability of fuzuloparib by fluconazole, which is a broad antifungal agent and a moderate inhibitor of CYP3A4. Methods: In this study, the effects of CYP3A4 inhibition on the pharmacokinetics of fuzuloparib were assessed in a total of 20 healthy Chinese male subjects in an open-label, two-period, single-sequence, crossover study. Results: Pharmacokinetic parameters, including the maximal plasma concentration (Cmax), the plasma concentration–time curve from time 0 to last measurable area under concentration (AUC0−t), and from time 0 to infinity (AUC0−∞), were increased by 32.4%, 104.5%, and 109.6%, with corresponding 90% confidence intervals of (23–43%), (93–116%), and (98–122%), respectively, when fluconazole was combined with fuzuloparib compared to fuzuloparib alone. There was also a slight increase in the incidence of treatment emergent adverse events, including hyperlipidemia and elevated aspartate transaminase. Conclusion: The fuzuloparib is 150 mg b.i.d in clinics use. Our results suggest that fuzuloparib could well be tolerated when administered as a single 20 mg oral dose alone or co-administered with 400 mg fluconazole in healthy male subjects. It is recommended to avoid using moderate CYP3A4 inhibitors together with fuzuloparib or instead of 50 mg when necessary.
- Subjects
PHARMACOKINETICS; POLY ADP ribose; FLUCONAZOLE; ASPARTATE aminotransferase; ANTIFUNGAL agents; CYTOCHROME P-450 CYP3A
- Publication
Cancer Chemotherapy & Pharmacology, 2022, Vol 89, Issue 1, p141
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-021-04376-1