优化了N,N-二甲基三胺的输注速率,以实现基于建模和模拟框架的目标迷幻强度
Emma Eckernäs1, Jeroen Koomen2, Christopher Timmermann3
1Unit for Pharmacokinetics and Drug Metabolism, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
CPT: pharmacometrics & systems pharmacology
|September 7, 2023
概括
设计N,N-二甲基三胺 (DMT) 输液协议需要仔细的建模. 种群的药理动力学/药理动力学模型为所需的迷幻强度提出了特定的剂量,但个人调整对于治疗疗效至关重要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 精神病学是一个精神病学.
- 计算建模计算建模
背景情况:
- N,N-二甲基三胺 (DMT) 是一种具有治疗精神疾病治疗潜力的迷幻化合物.
- 它的短半衰期需要持续输液策略来延长效果.
- 种群的药理动力学/药理动力学 (PopPK/PD) 建模是优化DMT输液协议的关键.
研究的目的:
- 使用PopPK/PD建模,根据所需的迷幻强度设计一个DMT输液协议.
- 为了比较连续变量和局限整数 PopPK/PD 模型用于协议设计.
- 评估模型选择对剂量建议的影响.
主要方法:
- 利用以前发表的连续变量模型和两个新的有限整数模型.
- 进行模拟以确定最佳的DMT胆固醇剂量和输液速率.
- 评估模型在达到目标迷幻强度等级 (7-9在0-10级) 的表现.
主要成果:
- 在不同的模型中,最佳剂量有所不同:16mg玻尿酸+1.4mg/分钟输液 (连续模型) 与14mg玻尿酸+1.2mg/分钟输液 (整数模型).
- 在所有模型中,在目标强度范围内模拟的比例很低 (<53%).
- 与连续模型相比,局限整数模型预测了较低的目标实现率和较高的超越率,特别是在规模边界.
结论:
- 由于模型的可变性,DMT输注方案需要进行个别剂量调整.
- 模型的选择 (连续与有界整数) 影响DMT剂量建议和预测结果.
- 对于精确的DMT治疗管理,需要进一步精细化PopPK/PD模型.
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