Results
In total, 51 p.Phe508del homozygous CF patients took lumacaftor and ivacaftor within this post-approval study. Eight to sixteen weeks after the initiation of treatment with CFTR modulators blood was taken to determine the serum concentrations of lumacaftor and ivacaftor (Supplementary Table S1). The median serum levels were 0.5 µg/ml for ivacaftor and 24 µg/ml for lumacaftor (Table 1), comparable to data from the EMA assessment report [8]. The serum samples contained on average 50-fold more lumacaftor than ivacaftor. Figure 1 shows the ivacaftor and lumacaftor concentrations for the 49 samples with less than 2 µg/ml ivacaftor, the remaining two samples contained high levels of ivacaftor of 9 and close to 4 µg/ml, respectively (Supplementary Table S1). The data in Figure 1 demonstrate the lack of any correlation between ivacaftor and lumacaftor levels.
The serum levels of lumacaftor, ivacaftor and the lumacaftor/ivacaftor ratio were tested for association with anthropometry, spirometry and CFTR activity determined within 0.1 – 2.5 hours past blood sampling. In 14 of 15 tests no significant correlations between drug serum levels and clinical parametrs. Neither body mass index, FEV1, sweat chloride concentration, Sermet score [10] of the NPD and the chloride secretory response [9] in the ICM (Table 2) correlated. One exceptions from this general finding was noted, i.e. the serum level of ivacaftor correlated with the decrease of sweat chloride concentration (P = 0.02). The correlation of the ratio of lumacaftor to ivacaftor levels with the increase of the Sermet score towards the normal range in the NPD showed a trend (P = 0.06).