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

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 (Cmin) levels or determination of the area under the curve (AUC). Hence, in this study the correlation between measured Cmin concentration and AUC was evaluated. Serial plasma samples, including Cmin, were drawn after administration of ETI in order to calculate the AUC and assess the correlation between the two parameters. A linear correlation between Cmin and AUC0-24h 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 Cmin levels.