A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project
Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are...
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Format: | Article |
Language: | English |
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Elsevier
2021-04-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332220312300 |
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doaj-129a0727d0ed4f99936df87ee088c84d |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nina Nauwelaerts Neel Deferm Anne Smits Chiara Bernardini Bart Lammens Peggy Gandia Alice Panchaud Hedvig Nordeng Maria Laura Bacci Monica Forni Domenico Ventrella Kristel Van Calsteren Anthony DeLise Isabelle Huys Michele Bouisset-Leonard Karel Allegaert Pieter Annaert |
spellingShingle |
Nina Nauwelaerts Neel Deferm Anne Smits Chiara Bernardini Bart Lammens Peggy Gandia Alice Panchaud Hedvig Nordeng Maria Laura Bacci Monica Forni Domenico Ventrella Kristel Van Calsteren Anthony DeLise Isabelle Huys Michele Bouisset-Leonard Karel Allegaert Pieter Annaert A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project Biomedicine & Pharmacotherapy In vitro In vivo PBPK Maternal medication Breastfeeding Lactation |
author_facet |
Nina Nauwelaerts Neel Deferm Anne Smits Chiara Bernardini Bart Lammens Peggy Gandia Alice Panchaud Hedvig Nordeng Maria Laura Bacci Monica Forni Domenico Ventrella Kristel Van Calsteren Anthony DeLise Isabelle Huys Michele Bouisset-Leonard Karel Allegaert Pieter Annaert |
author_sort |
Nina Nauwelaerts |
title |
A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project |
title_short |
A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project |
title_full |
A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project |
title_fullStr |
A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project |
title_full_unstemmed |
A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project |
title_sort |
comprehensive review on non-clinical methods to study transfer of medication into breast milk – a contribution from the conception project |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-04-01 |
description |
Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don’t always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBPK modelling to predict transfer of medication into the human milk. However, reliable data as input for PBPK models is often missing.The iterative development of in vitro, animal in vivo and PBPK modelling methods seems to be a promising approach. Human in vitro models will deliver essential data on the transepithelial transport of medication, whereas the combination of animal in vitro and in vivo methods will deliver information to establish accurate in vitro/in vivo extrapolation (IVIVE) algorithms and mechanistic insights. Such a non-clinical platform will be developed and thoroughly evaluated by the Innovative Medicines Initiative ConcePTION. |
topic |
In vitro In vivo PBPK Maternal medication Breastfeeding Lactation |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220312300 |
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doaj-129a0727d0ed4f99936df87ee088c84d2021-07-17T04:32:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-04-01136111038A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION projectNina Nauwelaerts0Neel Deferm1Anne Smits2Chiara Bernardini3Bart Lammens4Peggy Gandia5Alice Panchaud6Hedvig Nordeng7Maria Laura Bacci8Monica Forni9Domenico Ventrella10Kristel Van Calsteren11Anthony DeLise12Isabelle Huys13Michele Bouisset-Leonard14Karel Allegaert15Pieter Annaert16KU Leuven Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, O&N II Herestraat, 49 3000, Leuven, BelgiumKU Leuven Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, O&N II Herestraat, 49 3000, Leuven, BelgiumNeonatal Intensive Care Unit, University Hospitals Leuven, UZ Leuven, Neonatology, Herestraat 49, 3000, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, BelgiumDepartment of Veterinary Medical Sciences, University of Bologna, 40064, Ozzano dell'Emilia, BO, ItalyBioNotus, Galileilaan 15, 2845, Niel, BelgiumLaboratoire de Pharmacocinétique et Toxicologie, Centre Hospitalier Universitaire de Toulouse, FranceService of Pharmacy Service, Lausanne University Hospital and University of Lausanne, Switzerland; Institute of Primary Health Care (BIHAM), University of Bern, SwitzerlandPharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, PB. 1068 Blindern, 0316, Oslo, NorwayDepartment of Veterinary Medical Sciences, University of Bologna, 40064, Ozzano dell'Emilia, BO, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064, Ozzano dell'Emilia, BO, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064, Ozzano dell'Emilia, BO, ItalyUZ Leuven, Gynaecology and Obstetrics, Herestraat 49, 3000, Leuven, BelgiumNovartis Pharmaceuticals Corporation, Novartis Institutes for BioMedical Research, One Health Plaza, East Hanover, NJ, 07936, USAKU Leuven, Department of Clinical Pharmacology and Pharmacotherapy, ON II Herestraat 49 – bus, 521 3000, Leuven, BelgiumNovartis Pharma AG, Novartis Institutes for BioMedical Research, Werk Klybeck Postfach, Basel, CH-4002, SwitzerlandDepartment of Development and Regeneration, KU Leuven, Belgium; KU Leuven, Department of Clinical Pharmacology and Pharmacotherapy, ON II Herestraat 49 – bus, 521 3000, Leuven, Belgium; Department of Clinical Pharmacy, Erasmus MC, Rotterdam, the NetherlandsKU Leuven Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, O&N II Herestraat, 49 3000, Leuven, Belgium; Corresponding author at: O&N II Herestraat 49-box 921, 3000, Leuven, Belgium.Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don’t always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBPK modelling to predict transfer of medication into the human milk. However, reliable data as input for PBPK models is often missing.The iterative development of in vitro, animal in vivo and PBPK modelling methods seems to be a promising approach. Human in vitro models will deliver essential data on the transepithelial transport of medication, whereas the combination of animal in vitro and in vivo methods will deliver information to establish accurate in vitro/in vivo extrapolation (IVIVE) algorithms and mechanistic insights. Such a non-clinical platform will be developed and thoroughly evaluated by the Innovative Medicines Initiative ConcePTION.http://www.sciencedirect.com/science/article/pii/S0753332220312300In vitroIn vivoPBPKMaternal medicationBreastfeedingLactation |