Work

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

Year: 2021

Type: article

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

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2021.105913

Authors: Jennifer J Bonner, Howard Burt, Trevor N Johnson, Martin J Whitaker, John Porter, Richard J Ross

Institutions: Simcyp (United Kingdom), Diurnal (United Kingdom), University of Sheffield

Language: English

Topic: Adrenal Hormones and Disorders

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,850