Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects

IF 3 3区 医学 Q2 ONCOLOGY
Hyun Chul Kim, Eunsol Yang, Soyoung Lee, Jaeseong Oh, Myongjae Lee, ChaeEun Lee, Kyoung Soo Ha, Won Sik Lee, In-Jin Jang, Kyung-Sang Yu
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Abstract

Aim

Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects.

Methods

In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing.

Results

Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457–0.9094) and 1.02 (0.9088–1.1339) in Koreans, and 0.77 (0.6871–0.8609) and 0.96 (0.9017–1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated.

Conclusion

The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states.

Abstract Image

食物和种族对韩国、高加索和中国男性健康受试者服用新一代 PARP 抑制剂 Venadaparib 的药代动力学的影响
目的 Venadaparib是一种正在开发用于治疗胃癌的新一代聚(ADP-核糖)聚合酶抑制剂。本研究旨在评估健康的韩国人、高加索人和中国男性受试者单次口服 Venadaparib 后,食物和种族对其药代动力学(PKs)和安全性的影响。在一项开放标签、单剂量研究中,中国受试者仅在空腹状态下接受了 80 毫克 Venadaparib。结果每个族群有 12 名受试者完成了研究。韩国人和白种人在进食和禁食状态下的最大血浆浓度(Cmax)和从零时到最后可测量时间点的血浆浓度-时间曲线下面积(AUClast)的几何平均比(90%置信区间)分别为0.82(0.7457-0.9094)和1.02(0.9088-1.1339),白种人分别为0.77(0.6871-0.8609)和0.96(0.9017-1.0186)。三个种族群体之间的 Cmax(P 值 = 0.45)或 AUClast(P 值 = 0.30)差异无统计学意义。结论尽管在进食状态下Cmax下降,吸收延迟,但venadaparib的总体全身暴露量并未受到高脂餐的影响。韩国、高加索和中国受试者的 PK 曲线相似。在空腹和进食状态下,单次服用80毫克的文达帕利都是安全且耐受性良好的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
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