Development and verification of an endogenous PBPK model to inform hydrocortisone replacement dosing in children and adults with cortisol deficiency

The goal of hormone replacement is to mirror physiology. Hydrocortisone granules and modified release formulations are being developed optimise cortisol in the rare disease adrenal insufficiency. To facilitate clinical development, we built verified a physiologically based pharmacokinetic (PBPK) model for endogenous (hydrocortisone) healthy adults, children adults with predicted immediate-release hydrocortisone pharmacokinetics across dose range 0.5 20 mg, predicted/observed AUCs within 0.8 1.25-fold. also tightly parameters modified-release formulations, 1.25-fold after single multiple dosing. Predicted formulation (PK) 12 18-year olds showed PK be similar adults. This PBPK useful tool predict adult paediatric both immediate- develop dosing regimens.