FIGON DMD

Steffie Vonk

Amsterdam UMC

I am a pharmacist currently completing my residency in hospital pharmacy at the Amsterdam UMC. Concurrently, I am pursuing a PhD focused on the pharmacology of CFTR modulators in cystic fibrosis. My passion lies in working within multidisciplinary teams to find personalized treatment options that optimize patient outcomes. Through my residency, I have gained valuable experience in hospital pharmacy practices, while my research explores the pharmacokinetics and therapeutic effects of CFTR modulators. I am dedicated to contributing to the development of personalized treatments and enhancing patient care. With a strong foundation in pharmacological research and a patient-centered approach, I strive to make a positive impact in the field of clinical pharmacology.

Presentation: Real-world pharmacokinetics of elexacaftor, tezacaftor and ivacaftor in children with cystic fibrosis: the SYM-CF study.

Vonk S.E.M.¹, Dr. Terheggen-Lagro S.W.J.², Dr. Haarman E.G.², Prof. Dr. Maitland-van der Zee A.H.³, Prof. Dr. Mathôt R.A.A.¹, Dr. Kemper E.M.^1,4on behalf of the AMCD research group.
Department of ¹Hospital Pharmacy & Clinical Pharmacology, ²Pediatric Pulmonology and Allergy, ³Pulmonary Medicine, and ⁴Vascular Medicine, Amsterdam UMC.

The efficacy of elexacaftor-tezacaftor-ivacaftor (ETI) in children with cystic fibrosis (cwCF) is highly variable. Knowledge on the pharmacokinetics (PK) of ETI in cwCF may provide insight into the exposure-response relationship and its corresponding inter-patient variability (IIV). The aim of this study was to evaluate the PK of ETI in cwCF in a real-world setting.Thirty cwCF, aged 6-17 years, using ETI were included. Single blood samples were obtained during four regular outpatient hospital visits. Once, dried blood spot samples were taken at home at T=0, 4 and 8 hours after ingestion. Population-PK (popPK) models were developed using nonlinear mixed effects modelling. Area under the curve (AUC) was assessed using empirical Bayesian estimated PK parameters.PopPK models were developed successfully for ETI and metabolites. The IIV in AUC was high, caused by the variation in clearance and differences in ETI dose per age group. Despite this, AUCs of our cwCF in all age and dosing groups were comparable to their reference AUCs in the product information. PopPK models based on real-world data in cwCF were developed for ETI. These may be used to further study the response-efficacy relationship and its variability within cwCF, in order to improve its efficacy and safety.