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

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02438631

Acronym

PIANO

Enrollment

2000

Registered

2015-05-08

Start date

2015-02-28

Completion date

2028-12-31

Last updated

2022-09-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pregnancy

Keywords

placenta, placental passage

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).

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

OTHER

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Female * Age \> 18 * Signed informed consent * \>38 weeks pregnant

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
placental transfer	at delivery	1.) An ex-vivo placenta perfusion model will be used to estimate placental passage of drugs
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).
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).

Countries

Netherlands

Contacts

Primary ContactJ van Drongelen

joris.vandrongelen@Radboudumc.nl

Outcome results