Supplementary Material for: Evaluation of the effect of clobetasol propionate on circulating cortisol and growth velocity in children with atopic dermatitis: a modelling and simulation study

Background: Children with atopic dermatitis (AD) appear to have higher skin permeation, which may increase the risk of systemic adverse events following administration of potent topical corticosteroids, such as clobetasol propionate (CP). However, the assessment of dermal absorption in a controlled clinical trial in children is not feasible. Using model-based approaches, this study aimed to characterise stratum corneum (SC) and systemic exposure to CP following topical application of the cream formulation, and to investigate its effects on circulating cortisol levels and growth velocity in children with AD. Methods: Physiologically-based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PKPD) modelling were utilised to describe the dermal absorption of CP in a virtual cohort of paediatric patients (1 - 1 year old) without clinically relevant changes to circulating cortisol levels. In contrast to the systemic effects of oral corticosteroids, the short-term use of CP has no impact the growth velocity of paediatric subjects with AD.