Pengfei Du, Yao Long, Minhui Wang, Yunzhe Huang, Yaqin Wang, Xinyan Chen, Yuhong Lin, Jianbang Wu, Jie Shen, Yuanwei Jia
{"title":"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。","authors":"Pengfei Du, Yao Long, Minhui Wang, Yunzhe Huang, Yaqin Wang, Xinyan Chen, Yuhong Lin, Jianbang Wu, Jie Shen, Yuanwei Jia","doi":"10.1007/s00280-024-04672-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The time to maximum concentration (T<sub>max</sub>) was prolonged to 3 h and maximum concentration (C<sub>max</sub>) decreased by 18.6% on high-fat diets. 90% confidence intervals (CIs) of geometric mean ratios (GMRs) for C<sub>max</sub>, area under the concentration-time curve from time zero to time t (AUC<sub>0-t</sub>), and area under the concentration-time curve extrapolated to infinity (AUC<sub>0-∞</sub>) 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>This study was registered with chinadrugtrials.org.cn (identifier: CTR20221498).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":" ","pages":"251-257"},"PeriodicalIF":2.7000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of food on the pharmacokinetics and safety profiles of a new PARP inhibitor fuzuloparib capsules in healthy volunteers.\",\"authors\":\"Pengfei Du, Yao Long, Minhui Wang, Yunzhe Huang, Yaqin Wang, Xinyan Chen, Yuhong Lin, Jianbang Wu, Jie Shen, Yuanwei Jia\",\"doi\":\"10.1007/s00280-024-04672-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The time to maximum concentration (T<sub>max</sub>) was prolonged to 3 h and maximum concentration (C<sub>max</sub>) decreased by 18.6% on high-fat diets. 90% confidence intervals (CIs) of geometric mean ratios (GMRs) for C<sub>max</sub>, area under the concentration-time curve from time zero to time t (AUC<sub>0-t</sub>), and area under the concentration-time curve extrapolated to infinity (AUC<sub>0-∞</sub>) 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinical trial registration: </strong>This study was registered with chinadrugtrials.org.cn (identifier: CTR20221498).</p>\",\"PeriodicalId\":9556,\"journal\":{\"name\":\"Cancer Chemotherapy and Pharmacology\",\"volume\":\" \",\"pages\":\"251-257\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Chemotherapy and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00280-024-04672-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-024-04672-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Effect of food on the pharmacokinetics and safety profiles of a new PARP inhibitor fuzuloparib capsules in healthy volunteers.
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).
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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