Focus of research
[Forschungslinie 2]: Pharmacometric data analysis
“Pharmacokinetics of hydrocortisone in pediatric patients with congenital adrenal hyperplasia”
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders leading to decreased or no synthesis of cortisol. Low concentrations of cortisol leads to an imbalance in the steroid synthesis pathway, thereby, resulting in increased levels of androgens followed by symptoms, such as virilisation, hirsuitism and preoccus puberty. The prevalence of the more severe form is 1/15000 in newborns, but the less severe form is more prevalent (1/1000) and can sometimes be asymptomatic.
The recommended cortisol substitution therapy for growing paediatric patients constitutes of hydrocortisone. Drug monitoring in these patients may be problematic, since too high doses may increase the risk for Cushing’s syndrome, whereas too low doses may increase risk of adrenal crisis or disease progression. The therapeutic regimen is currently chosen based on empirical knowledge and is currently not standardised. We, therefore, see a need for improvement regarding the dosing regimen in this population to improve treatment outcome.
The aim of my PhD thesis will be to use a population-based pharmacokinetic approach to characterise the pharmacokinetics of hydrocortisone in paediatric patients from infants to adults. By relating the pharmacokinetics of hydrocortisone to disease-related biomarkers or patient characteristics, we hope to establish a pharmacokinetic-pharmacodynamic model, which later will be used in order to optimise therapy for paediatric patients with CAH.
The ultimate goal will be to establish a Therapeutic Drug Monitoring, which should be eval-
uated and optimally later could be used in the clinic.