Placental Passage and Disposition of Drugs: A Physiology-based Approach

Recruiting

• Conditions: Pregnancy

• Registration Number: NCT02438631
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-05-06
• Study First Submitted QC: 2015-05-07
• Study First Posted: 2015-05-08
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-09
• Last Update Posted: 2022-09-10
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 2000

Inclusion Criteria

• Female
• Age > 18
• Signed informed consent
• >38 weeks pregnant

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Exclusion Criteria

• Retained placenta
• HIV infected
• Known hepatitis C infection
• Multiple pregnancy
• Congenital birth defects child
• Sectio EXIT procedure

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
placental transfer	at delivery	1.) An ex-vivo placenta perfusion model will be used to estimate placental passage of drugs
in vitro experiments	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	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).

Trial Locations

Locations (1)

Radboud University Medical Centre; 🇳🇱 Nijmegen, Gelderland, Netherlands