基于生理学的成人和儿科生物制药建模,以解释lamotrigine即时释放吸收过程
Edilainy Rizzieri Caleffi-Marchesini1, Amanda Antunes Herling1, Julia Macente1
1Pharmacokinetics and Biopharmaceutics Laboratory, State University of Maringá, Maringá, PR, Brazil.
CPT: pharmacometrics & systems pharmacology
|November 2, 2023
概括
基于生理学的生物制药建模评估了lamotrigine.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物制药生物制药公司
- 药物开发 药物开发
背景情况:
- 基于生理学的生物制药建模 (PBBM) 有助于药物和配方开发,特别是对于具有成熟性药理动学的儿科群体.
- 拉莫特里金 (LTG) 是生物制药分类系统 (BCS) II 药物,需要对特殊人群进行生物制药风险评估.
- 儿童药物开发需要了解胃肠道 (GIT) 发育对药物吸收的影响.
研究的目的:
- 通过考虑儿科胃肠道 (GIT) 生理参数本体发生,评估低溶性拉莫特里金 (LTG) 的生物制药风险.
- 开发和验证成人和儿童 (2-12岁) 的口服生理学基础药理动力学 (PBPK) 和 PBBM 模型.
- 研究GIT生理参数对LTG体内溶解和吸收的影响.
主要方法:
- 开发并验证了使用GastroPlusTM用于成人和儿科 (2-12岁) 人群的口服生理学基础的药理动力学 (PBPK) 和 PBBM模型.
- 进行敏感性分析以评估生物制药性质和GIT生理参数.
- 模拟成人 (200毫克) 和儿童 (5毫克/千克,最大200毫克) 的高剂量场景,以评估最坏情况下的生物制药风险.
主要成果:
- 灵敏度分析显示,胃过境时间是对LTG生物制药产品影响最大的参数.
- 在胃肠液体体积和影响LTG体内溶解的剂量体积之间没有观察到显著的干扰.
- 该研究提出了一个假设,即LTG在体外可能表现出BCS II的特征,但在体内可能表现出BCS I的行为.
结论:
- 胃过渡时间是影响儿科群体中拉莫特里金 (LTG) 生物制药性能的关键因素.
- 开发的 PBBM 提供了一个针对特定人群和临床条件量身定制的基于模型的精确剂量的框架.
- 这种建模方法可以指导对各种释放特征的评估,以优化LTG在成人和儿童的体内表现.
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