open-systems-pharmacology / levonorgestrel

Whole-body PBPK model of levonorgestrel with and without ethinyl estradiol as CYP3A4 DDI victim drug

Levonorgestrel

Whole-body PBPK model of Levonorgestrel as well as ethinyl estradiol

This repository contains:

• a PK-Sim project (*.pksim5) file of the current PBPK model(s)

This levonogrestrel model is intended to be used as victim drug in CYP3A4-mediated drug-drug interactions (DDI) when orally administered either alone or in combination with ethinyl estradiol in healthy and obese women.

The model incorporates dynamic changes in SHBG protein-binding, via an Emax model, observed during long-term use of levonogrestrel and ethinyl estradiol.

The presented model represents an original model development project presented by Cicali et al. [1]. A complete summary of model development and application can be found in this manuscript and respective supplemental materials.

Code of conduct

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Contribution

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License

The model code is distributed under the GPLv2 License.

References

[1] [Cicali, B. et al. Quantitative assessment of levonorgestrel binding partner interplay and drug-drug interactions using physiologically based pharmacokinetic modeling. CPT:Pharmacometrics and Systems Pharmacology. accepted (2020).]