桥梁人群的药理动力学和半机械吸收模拟APX333030的吸收
Larissa L Silva1, Robert E Stratford1, Richard Messmann2
1Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indiana, Indianapolis, USA.
CPT: pharmacometrics & systems pharmacology
|October 26, 2023
概括
这项研究详细介绍了APE1/Ref-1抑制剂APX3330的药理动力学,揭示了食物通过增加滞后时间来延迟其吸收. 在癌症患者中,APX3330的口服清除率高于健康个体.
科学领域:
- 药理学和药物开发领域
- 生物化学 生化学
- 临床药理动力学 临床药理动力学
背景情况:
- APX3330是一种APE1/Ref-1的选择性抑制剂,在肝炎,癌症和眼部疾病中具有治疗潜力.
- 该药物以子的形式口服,然后转化为基的形式.
研究的目的:
- 在口服后描述APX3330的药理动力学.
- 为了研究食物对APX3330吸收和排放的影响.
- 为了比较健康人和癌症患者之间的药理动力学参数.
主要方法:
- 非线性混合效应建模 (Monolix) 用于分析健康日本男性和癌症患者的血度.
- 开发了一种半生理学药理动力学模型 (Gastroplus),以模拟食物对溶解和吸收的影响.
- 估计了药理动力学参数,并评估了共变效应,包括食物和疾病状态.
主要成果:
- 一个具有第一阶吸收和滞后时间的两部分模型最好地描述了健康男性的数据.
- 食物摄入量增加了80%的滞后时间,并将吸收控制从溶解转移到胃排空.
- 在癌症患者中,明显的口服清除 (CL/F) 高出41%,可能是由于血清白蛋白降低.
结论:
- 食物显著延迟APX3330的吸收,可能是由于转化和胃肠道过境的改变.
- 在癌症患者中,更高的口服清除值得进一步调查,可能与专蛋白水平有关.
- 未来的研究应该区分APX3330的和基形式的药理动力学.
相关概念视频
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