Data from: The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels: human in vivo measurements

We optically measured effects of orally available ivacaftor (Kalydeco®) on
sweat rates of identified glands in 3 R117H subjects, each having a unique
set of additional mutations, and compared them with 5 healthy control
subjects tested contemporaneously. We injected β-adrenergic agonists
intradermally to stimulate CFTR-dependent ‘C-sweat’ and methacholine to
stimulate ‘M-sweat’, which persists in CF subjects. We focused on an
R117H-7T/F508del subject who produced quantifiable C-sweat off ivacaftor
and was available for 1 blinded, 3 off ivacaftor, and 3 on ivacaftor
tests, allowing us to estimate in vivo fold-increase in sweat rates
produced by ivacaftor’s effect on the open probability (PO) of R117H-CFTR.
Measured sweat rates must be corrected for sweat losses. With estimated
sweat losses of 0.023 to 0.08 nl·gland-1·min-1, ivacaftor increased the
average C-sweat rates 3-7 fold, and estimated function as % of WT were
4.1-12% off ivacaftor and 21.9-32% on ivacaftor (larger values reflect
increased loss estimates). Based on single tests, an R117H-7T/ R117H-7T
subject showed 6-9% WT function off ivacaftor and 28-43% on ivacaftor.
Repeat testing of an R117H-5T/F508del subject detected only trace
responding to ivacaftor. We conclude that in vivo, R117H PO is strongly
increased by ivacaftor, but channel number, mainly determined by variable
deletion of exon 10, has a marked influence on outcomes.