小分子药物在炎症性肠病中的吸收和目前在生理学基础的药物动力学模型中的实施
Jonas Langeraert1, Elke Gasthuys1, An Vermeulen1
1Laboratory of Medicinal Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
炎症性肠病 (IBD) 由于生理变化而改变药物吸收. 基于生理学的药理动力学 (PBPK) 模型在预测IBD患者药物吸收方面表现有前途,但需要进一步开发.
科学领域:
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
- 药物开发 药物开发
背景情况:
- 炎症性肠病 (IBD),包括克罗恩病 (CD) 和性结肠炎 (UC),涉及慢性胃肠道炎症.
- IBD患者通常具有需要口服药物的并存条件,使药物吸收成为关键问题.
- 在IBD中变化的胃肠道生理学可以显著影响口服药物的吸收.
研究的目的:
- 审查影响IBD患者口服药物吸收的生理因素.
- 批判性地检查生理学基础的药理动力学 (PBPK) 建模在预测IBD药物吸收中的实用性.
- 确定有关IBD药物吸收的当前研究中的挑战和局限性.
主要方法:
- 关于IBD中小肠和大肠之间生理差异的文献综述.
- 分析影响药物吸收的因素:光体积,pH值,传输时间,胆盐,微生物群,表面积,透性和酶/载体.
- 对PBPK建模研究进行批判性检查,这些研究纳入了IBD病理生理学,并通过临床数据验证了预测.
主要成果:
- IBD显著改变胃肠道生理学,影响药物吸收参数,在研究中具有很高的异质性.
- 与健康志愿者相比,IBD患者对这些因素的直接评估很少.
- 结合IBD病理生理学的PBPK模型在预测口服药物吸收方面取得了部分成功,但尚未可通用.
结论:
- 在IBD的生理变化对口服药物吸收预测提出了挑战.
- PBPK建模提供了一种有价值的方法,但需要更多的数据和验证,以便在IBD中得到更广泛的应用.
- 需要进一步的研究来完善PBPK模型,并改善对IBD患者药物处置的理解.
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