两种SHR7280制剂（干混悬剂和片剂）单剂量口服给药在健康中国志愿者中的相对生物利用度。

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

作者信息

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

机构信息

The Second School of Clinical Medicine, Guangzhou Medical University, Guangzhou, China.

Phase I Clinical Trial Center, The Second Affiliated Hospital, Guangzhou Medical University, No. 63, South Road of Aisa Games City, Panyu District, Guangzhou, 511400, China.

出版信息

Clin Drug Investig. 2025 Sep;45(9):643-650. doi: 10.1007/s40261-025-01470-7. Epub 2025 Aug 8.

DOI:10.1007/s40261-025-01470-7

PMID:40779283

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) and area under the plasma concentration-time curve from time 0 to t (AUC) and from time 0 to infinity (AUC) between the dry suspension of SHR7280 and its tablets were calculated as follows: C-101.90% (90% CI 79.50-130.62), AUC-111.58% (90% CI 91.71-135.76), and AUC-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).

摘要

背景

SHR7280是一种口服小分子促性腺激素释放激素（GnRH）拮抗剂，可开发为治疗激素依赖性疾病的治疗药物，包括前列腺癌、乳腺癌和卵巢癌。正在开发SHR7280干混悬剂，为老年患者、使用营养管的患者以及无法吞咽固体剂型的患者提供另一种给药方式。

目的

本研究评估了健康中国志愿者单次服用SHR7280干混悬剂和片剂后的相对生物利用度、药代动力学（PK）和安全性。

方法

本研究采用随机、开放、双制剂、双序列、双周期、双交叉设计。采用液相色谱-串联质谱（LC-MS/MS）测定血浆药物浓度。使用Phoenix WinNonlin（版本8.3.4）软件通过非房室分析计算SHR7280两种制剂的主要PK参数。共有16名健康参与者被随机分配接受200mg SHR7280片剂（n = 8）或干混悬剂（n = 8）。

结果

计算了SHR7280干混悬剂与其片剂之间血浆中药物最大浓度（C）、血浆浓度-时间曲线从0到t（AUC）以及从0到无穷大（AUC）的几何最小二乘均值比（90%置信区间[CI]），结果如下：C为101.90%（90%CI 79.50-130.62），AUC为111.58%（90%CI 91.71-135.76），AUC为111.44%（90%CI 91.70-135.43）。共有9名（56.3%）受试者出现治疗期间出现的不良事件（TEAE）。