在老鼠和非人类灵长类动物中的OCE-205:药理动力学和药理动力学分析
Stan Bukofzer1, Geoff Harris2, Edward E Cable2
1Ocelot Bio, Inc., Redwood City, CA, USA.
Current research in pharmacology and drug discovery
|August 23, 2023
概括
一种新OCE-205通过选择性向血管压素受体,显示出治疗肝硬化并发症的潜力. 在老鼠和子中进行的临床前研究表明,与terlipressin相比,它有效提高血压,具有有利的安全性.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 心血管研究研究心血管研究
背景情况:
- 目前对不补偿性肝硬化并发症的治疗方法,特别是肝综合征-急性损伤 (HRS-AKI),是不理想的.
- 特里普林素是一种V1a激动剂,用于HRS-AKI,但具有显著的副作用.
- 需要针对血管压素系统的新药,以提高安全性和有效性.
研究的目的:
- 为了评估OCE-205的体内药理动力学和药理动力学特性,OCE-205是一种新的混合V1a激动剂/对抗剂.
- 在临床前模型中,比较OCE-205与阿尔金因血压素 (AVP) 和特里普林素的疗效和安全性.
主要方法:
- OCE-205通过静脉注射 (IV) 或皮下注射 (SC) 在健康的老鼠和子中进行了注射.
- 氨酸血压素 (AVP) 和特里普林素作为比较剂.
- 测量了药理动力学参数 (血度) 和药理动力学效应 (平均动脉压,血液乳酸).
主要成果:
- 在小鼠和子中,OCE-205在IV和SC给药后显示出可预测的血水平.
- OCE-205以剂量依赖和持续的方式显著增加了平均动脉压 (MAP),特别是在SC给药后.
- 与AVP不同,OCE-205没有显著增加血液乳酸盐水平,并且在两种物种中都能很好地容忍.
结论:
- OCE-205表现出V1a选择性部分激动剂活性,具有潜在的有利的安全性.
- 它的药理动力学和药理动力学特性表明,它在治疗与肝硬化相关的心血管并发症方面具有潜在的实用性.
- 需要进一步研究OCE-205作为HRS-AKI和相关疾病的治疗剂.
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