Abstract
This study aimed to characterize the PK of ivacaftor-lumacaftor using population PK and inter-individual variability (IIV) in 60 patients from 5 different CF centres. Secondary objectives were to identify patient characteristics and bidirectional interactions responsible for IIV. In this retrospective observational study, clinical data and plasma samples of ivacaftor, lumacaftor and M1 and M6 metabolite levels were collected from 60 CF patients on standard ivacaftor-lumacaftor combination (125mg+200mg). Cmax concentrations of ivacaftor - lumacaftor were >10 fold lower than expected. The one-way ANOVA indicated that the patient site had a significant effect on the Cmax values of ivacaftor M1, ivacaftor M6, and lumacaftor (p<0.001, p<0.001, and p<0.001, respectively). A significant site effect was identified on Tmax for the M1 and M6 metabolites of ivacaftor (p=0.001 and p=0.004, respectively). The Spearman’s rho test indicated that patient weight and age have a significant effect on the Cmax of lumacaftor (p=0.003 and p<0.001, respectively) and ivacaftor M1 (p=0.020 and p<0.001, respectively). Age (p<0.001) was found to have a significant effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p=0.026). Based on the current PK sampling there is high IIV based on the greater than ten-fold variation in PK concentrations among the different treatment groups. The impact of patient demographics on the bidirectional PK descriptors that is Cmax and Tmax large inter-patient variability was observed in PK among CF patients.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 362.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020