Lactation-PBPK-model

Whole body PBPK model to quantitatively predict ondansetron transfer into breast milk.

Repository Files

Within this repository, we built a lactation PBPK model using an ondansetron pregnancy model [1-2] as a template. This model is evaluated using in vivo concentration data from plasma and breast milk in lactating women. Predictions were based on a virtual lactating population we developed that included anatomic and physiological changes that occur after delivery. Details on model building and evaluation have been published previously [3].

This repository contains the MoBi^® file (.mbp3) with the lactation model structure. Please note that this model is not correctly parameterized in terms of the postpartum anatomy and physiology; it just contains the spatial structure and passive transports building blocks of the lactation model.

The postpartum/lactation anatomy and physiology is not integrated in the official release of the PK-Sim^® database. Therefore, a database file (.sqlite) with the anatomical and physiological parameters of postpartum individuals is distributed within this repository. There are two database files provided in this repository:

• PKSimDB_v9.sqlite is compatible with the PK-Sim^® portable version 9.1
• PKSimDB_v11.sqlite is compatible with the PK-Sim^® portable version 11

Please note that for using the database file .sqlite file in PK-Sim^® portable it needs to be renamed to PKSimDB.sqlite.

The database file (.sqlite) can be combined with the MoBi^® file (.mbp3) for importing and running a postpartum population simulation in the portable version of PK-Sim^® as described in detail in the supplement of the article by Job et al. [3].

Version Information

PK-Sim^® Version 9.1 MoBi^® Version 9.1

License

The model is distributed under the GPLv2 License.

References

[1]Dallmann A, Ince I, Coboeken K, Eissing T, Hempel G. A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Clin Pharmacokinet. Jun 2018;57(6):749-768. doi:10.1007/s40262-017-0594-5.

[2]Open-Systems-Pharmacology/Pregnancy-Models.

[3]Job KM, Dallmann A, Parry S, et al. Development of a Generic Physiologically Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk. Clin Pharmacol Ther. Jan 25 2022;doi:10.1002/cpt.2530.