Relative Bioavailability of Single-Dose Oral Administration of Two SHR7280 Formulations (Dry Suspension and Tablets) in Healthy Chinese Volunteers.

IF 2.7 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI:10.1007/s40261-025-01470-7

Xian Liu, Ruzhai Qin, Chang Shu, Kai Shen, Xi Li, Lingyu Ma, Xiaomei Li, Lanping Li, Jiao Peng, Dongxiang Huang, Sihan Chen, Zhihong Xie, Lika Ye, Lian Duan

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引用次数: 0

Abstract

Background: SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.

Objective: This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.

Methods: A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (n = 8) or dry suspension (n = 8) formulation.

Results: The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (C_max) and area under the plasma concentration-time curve from time 0 to t (AUC_0-t) and from time 0 to infinity (AUC_0-∞) between the dry suspension of SHR7280 and its tablets were calculated as follows: C_max-101.90% (90% CI 79.50-130.62), AUC_0-t-111.58% (90% CI 91.71-135.76), and AUC_0-∞-111.44% (90% CI 91.70-135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).

Conclusions: The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.

Trial registration: ClinicalTrials.gov (NCT05868057; 22 May 2023).

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两种SHR7280制剂（干混悬剂和片剂）单剂量口服在中国健康志愿者中的相对生物利用度

背景：SHR7280是一种口服小分子促性腺激素释放激素（GnRH）拮抗剂，可作为治疗激素依赖性疾病的药物，包括前列腺癌、乳腺癌和卵巢癌。正在开发SHR7280干悬浮液制剂，为order患者、使用营养管的患者和无法吞咽固体剂型的患者提供另一种给药模式。目的：本研究评估SHR7280干混悬剂和片剂在中国健康志愿者中单剂量给药的相对生物利用度、药代动力学（PK）和安全性。方法：采用随机、开放、双准备、双序列、双周期、双交叉设计。采用液相色谱-串联质谱法（LC-MS/MS）测定血浆药物浓度。采用Phoenix WinNonlin （version 8.3.4）软件进行非区室分析，计算SHR7280两种配方的主要PK参数。共有16名健康参与者随机接受SHR7280 （200 mg）片剂（n = 8）或干悬浮液（n = 8）制剂。结果:几何最小二乘均值比率(90%可信区间[CI])最大血浆中的药物浓度(Cmax)和血浆浓度时间曲线下的面积从0到t (AUC0-t)和时间0到无穷大(AUC0 -∞)干暂停SHR7280和平板电脑之间的计算如下:Cmax - 101.90% (90% CI 79.50 - -130.62), AUC0 - t - 111.58% (90% CI 91.71 - -135.76),和AUC0 -∞-111.44% (90% CI 91.70 - -135.43)。共有9名（56.3%）受试者出现治疗不良事件（teae）。结论：SHR7280片的生物利用度与干混悬液相当。两种制剂的安全性均较好。未见严重不良事件或药物不良反应。试验注册：ClinicalTrials.gov (NCT05868057；2023年5月22日)。

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

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.