Power of integrating PBPK with PBBM (PBPK-BM): a single model predicting food effect, gender impact, drug-drug interactions and bioequivalence in fasting & fed conditions

Abstract

1. Over the past few years, PBPK and PBBM modelling have proven their significance in drug development. PBPK modelling is traditionally used to predict drug-drug interactions, exposures in special populations whereas PBBM modelling is a part of PBPK modelling that is used for a range of biopharmaceutics applications.

2. Because of these differences in utilities, often PBPK and PBBM models are developed separately. When both models are combined, they serve multiple purposes through unified model. In the present case, an integrated PBPK-PBBM model for an IR product has been utilised for bioequivalence prediction in fasting & fed conditions, evaluating gender impact and food effect, prediction of drug-drug interactions.

3. Model was built using physicochemical properties, enzymes and transporter kinetics, bio-predictive dissolution and has been validated with passing and failed pilot BE studies. The validated model predicted pivotal bioequivalence outcomes in fasting & fed conditions accurately, predicted gender impact and food effect in line with literature. Drug-drug interactions arising from transporter and metabolising enzymes were predicted accurately.

4. Overall, this work demonstrates the utility of combining PBPK and PBBM model that can yield a single model which can be used for multiple purposes, regulatory justifications and can reduce regulatory review timelines.

Keywords:

• PBPK
• PBBM
• gender impact
• food effect
• bioequivalence
• Drug-drug interactions

Acknowledgements

Authors would like to thank Dr. Reddy’s Laboratories Ltd., for providing assistance and support to publish this work.

Disclosure statement

All the authors are employees of Dr. Reddy’s Laboratory Ltd. and report that there are no competing interests to declare. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This research article is sponsored by Dr. Reddy’s Laboratories Ltd.