Physiologically Based Pharmacokinetic Modelling and Simulation to Predict the Plasma Concentration Profile of Doxorubicin

Doxorubicin (DOX) is still an important anticancer agent despite its tricky pharmacokinetics (PK) and toxicity potential. The advent of systems pharmacology enables the construction of PK models able to predict the concentration profiles of drugs and shed light on the underlying mechanisms involved in PK and pharmacodynamics (PD). By utilizing existing published data and by analysing two clinical case studies we attempt to create physiologically based pharmacokinetic (PBPK) models for DOX using widely accepted methodologies. Based on two different approaches on three different key points we derived eight plausible models. The validation of the models provides evidence that is all performing as designed and opens the way for further exploitation by integrating metabolites and pharmacogenomic information.

Automated summary

This article constructs PBPK models for DOX using systems pharmacology approach and analyses eight plausible models based on existing data and two clinical case studies. The validation of the models supports their design and provides a basis for further research.