Placental Passage and Disposition of Drugs: A Physiology-based Approach
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- placental transfer
研究概览
简要总结
The investigators aim to integrate the outcomes in physiology-based pharmacokinetic (PBPK) models to put the generated data into context with medical conditions that require maternal or fetal drug therapy (e.g. HIV). These models will be validated with available 'real-life' maternal and fetal PK data, such as data from the PANNA network.
PBPK models of drug therapy during pregnancy will provide a powerful tool to 1.) assist in designing rational dosing adjustments, 2.) prevent intervention-based research in pregnant women in the future, and 3.) guide future development of new molecular entities (e.g. preventing heavy investment in drugs with high predicted fetal exposure and potentially toxic effects in utero).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age > 18
- •Signed informed consent
- •>38 weeks pregnant
排除标准
- •Retained placenta
- •HIV infected
- •Known hepatitis C infection
- •Multiple pregnancy
- •Congenital birth defects child
- •Sectio EXIT procedure
结局指标
主要结局
placental transfer
时间窗: at delivery
1.) An ex-vivo placenta perfusion model will be used to estimate placental passage of drugs
in vitro experiments
时间窗: at delivery
Furthermore, in vitro experiments will be conducted to estimate the pharmacodynamic effects of drugs on the placental barrier function itself (e.g. whether exposure to drugs can induce/reduce the expression of enzymes and transporters, as has been reported for several organs, such as the liver, intestine and kidney).
histological profiling
时间窗: at delivery
Histological and protein profiling experiments will be conducted to investigate factors that may influence the placental passage and disposition of drugs (e.g. the abundance, localization and inter-individual variation of expression of enzymes and transporters).
次要结局
未报告次要终点