Investigation of a fully mechanistic physiologically based pharmacokinetics model of absorption to support predictions of milk concentrations in breastfeeding women and the exposure of infants: A case study for albendazole | Semantic Scholar (2024)

The findings of this study support the recommendation made by the authors who reported the results of the clinical lactation study, that when put into context of safety data currently available in children, PQ should not be withheld in lactating women as it is unlikely to cause adverse events in breastfeeding infants greater than or equal to 28 days old.

This study aims to assess the predictive performance of an integrated ‘log transformed phase‐distribution’ lactation model within a PBPK platform that utilizes the physicochemical properties of four basic drugs to predict the milk‐to‐plasma (M/P) ratio.

Investigation of the possibility of integrating milk-to-plasma (M/P) ratio predictive algorithms within the physiologically-based pharmacokinetic (PBPK) approach to facilitate and extend the application of PBPK models during drug development in high-throughput screening and in different clinical settings.

A high‐risk period of exposure at 2–4 weeks of age was identified and can inform future drug‐in‐milk risk assessments, and existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency.

Pregnancy‐related changes in uridine 5′‐diphospho‐glucuronosyltransferase and transport functions are emerging, and incorporation of such changes in current physiologically based pharmacokinetic modeling software is in progress.

The results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately and could be useful for new oral drug development.

PBPK models and PBBMs have remarkably contributed to model-informed drug development (MIDD) such as anticipating clinical PK outcomes affected by extrinsic and intrinsic factors in general and specific populations.

After an oral dose of 400 mg, ABZ and ABSX attain low concentrations in breast milk that are unlikely to be considered harmful for the breastfed infant.

The results indicated that milk protein binding and fat partitioning can make a substantial contribution in determining M/P, and predictions of M/p made without considering these factors may be misleading.

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