Considerations for physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling to facilitate drug development in obese and related specific populations

PBPK-PD modelling is widely used in the pharmaceutical industry for model-informed drug development by assessing for instance drug-drug interactions, dosing predictions, but also dose recommendations in pregnancy, paediatric patients, or for mild, moderate, and severe hepatic impaired patient populations (classified based on Child-Pugh score). PBPK-PD can be used to assess how known physiological differences driving changes in pharmacokinetics and pharmacodynamics in overweight, obesity, and morbidly obesity which are common underlying co-morbidity for fatty liver and metabolic dysfunction-associated steatohepatitis (MASH). Physiology changes relative to a known control (typical healthy volunteer data) can often be used to adjust established PBPK-PD models easily. While established PBPK-PD models for the above-mentioned populations have been verified with available exposure, drug-drug interaction data, and were linked to expected pharmacodynamic effects, key data gaps could be identified.