Effect of food on the pharmacokinetics and safety profiles of a new PARP inhibitor fuzuloparib capsules in healthy volunteers.

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-04 DOI:10.1007/s00280-024-04672-6
Pengfei Du, Yao Long, Minhui Wang, Yunzhe Huang, Yaqin Wang, Xinyan Chen, Yuhong Lin, Jianbang Wu, Jie Shen, Yuanwei Jia
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Abstract

Purpose: This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules.

Methods: A randomized, open-label, two-cycle, two-sequence, crossover clinical trial was conducted. 20 subjects were randomly assigned to 2 groups at a 1:1 ratio. The first group subjects were orally administered 150 mg fuzuloparib capsules under fasting condition in first dosing cycle. The same dose of fuzuloparib capsules were taken under postprandial state after a 7-day washout period. The second group was reversed. 3 ml whole blood was collected at each blood collection point until 72 h post dose. PK parameters were calculated. Furthermore, safety assessment was performed.

Results: The time to maximum concentration (Tmax) was prolonged to 3 h and maximum concentration (Cmax) decreased by 18.6% on high-fat diets. 90% confidence intervals (CIs) of geometric mean ratios (GMRs) for Cmax, area under the concentration-time curve from time zero to time t (AUC0-t), and area under the concentration-time curve extrapolated to infinity (AUC0-∞) after high-fat meal were 71.6-92.6%, 81.7-102.7% and 81.6-102.5%, respectively. All treatment-emergent adverse events (TEAEs) were grade 1; No serious adverse events (SAEs), serious unexpected suspected adverse reaction (SUSAR) or deaths were reported.

Conclusion: Food decreased the absorption rate and slowed time to peak exposure of fuzuloparib capsules, without impact on absorption extent. Dosing with food was found to be safe for fuzuloparib capsules in this study.

Clinical trial registration: This study was registered with chinadrugtrials.org.cn (identifier: CTR20221498).

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食物对健康志愿者服用新型 PARP 抑制剂 fuzuloparib 胶囊的药代动力学和安全性的影响。
目的:本研究评估了食物对氟唑帕利胶囊药代动力学(PK)和安全性的影响:进行了一项随机、开放标签、两周期、两序列、交叉临床试验。20名受试者按1:1的比例随机分配到两组。第一组受试者在第一个给药周期中空腹口服150毫克福唑帕利胶囊。经过 7 天的冲洗期后,在餐后状态下服用相同剂量的 fuzuloparib 胶囊。第二组则相反。每个采血点采集 3 毫升全血,直至服药后 72 小时。计算 PK 参数。此外,还进行了安全性评估:结果:在高脂饮食中,达到最大浓度(Tmax)的时间延长至 3 小时,最大浓度(Cmax)降低了 18.6%。高脂餐后Cmax、从零时到t时的浓度时间曲线下面积(AUC0-t)和外推至无穷大的浓度时间曲线下面积(AUC0-∞)的几何平均比(GMR)的90%置信区间(CIs)分别为71.6%-92.6%、81.7%-102.7%和81.6%-102.5%。所有治疗突发不良事件(TEAEs)均为1级;无严重不良事件(SAEs)、严重意外疑似不良反应(SUSAR)或死亡报告:结论:食物降低了福唑帕利胶囊的吸收率,减缓了达到峰值暴露的时间,但对吸收程度没有影响。本研究发现,与食物一起服用福唑帕利胶囊是安全的:本研究已在chinadrugtrials.org.cn注册(标识符:CTR20221498)。
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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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