AUC, Cmax, and half-life of tezacaftor-ivacaftor
real-world compared to reported values
In table 3 the average AUC values per age and dosing group are shown and
compared with the corresponding reported value in the product
information. (3) The variability is large within age groups, as
demonstrated by the large SD with corresponding coefficients of
variation (CV) between 16-88%. The AUC differs per age group, as
children 6-11y ≥ 30kg tend to have a higher AUC value than children from
other age groups. Difference in average AUC versus reported values in
the product information was less than ±17%, except for tezacaftor in
12-17y and ivacaftor in 6-11y ≥ 30kg with -32% and 48% difference,
respectively.
In table 4 mean (SD) Cmax and half-lives per age and
dosing group are presented for tezacaftor-ivacaftor in relation to their
reported adolescent/adult values in the product information and
registration document. (3, 4) Children with age 6-11y with a body weight
≥30kg tend to have a higher mean Cmax, and in the age
group 6-11y < 30kg the mean half-lives tend to be shorter.
Overall the pooled mean Cmax seems slightly lower for
tezacaftor in our pediatric data, compared to the reported adult values.
(3) For tezacaftor the half-lives in children tend to be shorter
compared to the reported adult values. (3) For ivacaftor
Cmax are overall comparable and half-lives tend to be
higher than the reported values in adults, except for the age group
6-11y < 30kg. (3)