Correlation between trough concentration and AUC for elexacaftor, tezacaftor and ivacaftor

Steffie E M Vonk; Josje Altenburg; Ron A A Mathôt; E Marleen Kemper; Amsterdam Mucociliary Clearance Disease (AMCD) Research Group

doi:10.1016/j.jcf.2024.03.010

Correlation between trough concentration and AUC for elexacaftor, tezacaftor and ivacaftor

J Cyst Fibros. 2024 Mar 16:S1569-1993(24)00038-9. doi: 10.1016/j.jcf.2024.03.010. Online ahead of print.

Authors

Steffie E M Vonk¹, Josje Altenburg², Ron A A Mathôt³, E Marleen Kemper⁴; Amsterdam Mucociliary Clearance Disease (AMCD) Research Group

Affiliations

¹ Amsterdam UMC location University of Amsterdam, Department of Hospital Pharmacy & Clinical Pharmacology, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address: s.e.vonk@amsterdamumc.nl.
² Amsterdam UMC location University of Amsterdam, Department of Pulmonary Medicine, Meibergdreef 9, Amsterdam, the Netherlands.
³ Amsterdam UMC location University of Amsterdam, Department of Hospital Pharmacy & Clinical Pharmacology, Meibergdreef 9, Amsterdam, the Netherlands.
⁴ Amsterdam UMC location University of Amsterdam, Department of Hospital Pharmacy & Clinical Pharmacology, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands.

PMID: 38494378
DOI: 10.1016/j.jcf.2024.03.010

Abstract

Therapeutic drug monitoring (TDM) of elexacaftor, tezacaftor, ivacaftor (ETI) could be a useful tool to increase efficacy and decrease the risk of adverse effects in people with Cystic Fibrosis (pwCF). It is however unclear whether drug exposure should be monitored by assessment of trough (C_min) levels or determination of the area under the curve (AUC). Hence, in this study the correlation between measured C_min concentration and AUC was evaluated. Serial plasma samples, including C_min, were drawn after administration of ETI in order to calculate the AUC and assess the correlation between the two parameters. A linear correlation between C_min and AUC_0-24h was found, with Pearson's r correlation coefficients of 0.963, 0.908 and 0.860 for elexacaftor, tezacaftor and ivacaftor, respectively. Exposure of ETI may be monitored by assessment of C_min levels.

Keywords: Area under the curve; CFTR modulators; Elexacaftor-tezacaftor-ivacaftor; Therapeutic drug monitoring; Trough concentration.