The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study

J Cyst Fibros. 2017 Jan;16(1):132-138. doi: 10.1016/j.jcf.2016.07.006. Epub 2016 Jul 26.


Background: Ivacaftor has produced significant improvement in certain individuals with cystic fibrosis (CF), though the full metabolic effects of treatment remain unknown. Abnormalities in fatty acid metabolism have previously been shown to be a characteristic of CFTR dysfunction. We hypothesized that as a reflection of this clinical improvement, ivacaftor would improve plasma fatty acid levels and decrease urine prostaglandin E metabolite levels.

Methods: This study analyzed plasma fatty acid levels and urine prostaglandin E metabolites (PGE-M) in 40 subjects with CF participating in the G551D observational (GOAL) study who demonstrated response to the medication by a significant decrease in sweat Cl levels. Paired samples were analyzed before and after 6months of ivacaftor treatment.

Results: Linoleic acid and docosahexaenoic acid levels, which are typically low in individuals with CF, did not significantly increase with ivacaftor treatment. However, arachidonic acid levels did decrease with ivacaftor treatment and there was a significant decrease in the arachidonic acid metabolite PGE-M as measured in the urine [median: before treatment 17.03ng/mg Cr; after treatment 9.06ng/mg Cr; p<0.001]. Furthermore, there were fatty acid age differences observed, including pediatric participants having significantly greater linoleic acid levels at baseline.

Conclusion: Ivacaftor reduces inflammatory PGE without fully correcting the plasma fatty acid abnormalities of CF. Age-related differences in fatty acid levels were observed, that may be a result of other clinical factors, such as diet, clinical care, or drug response.

Keywords: Cystic fibrosis; Fatty acids; Ivacaftor; Prostaglandin E.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aminophenols / administration & dosage*
  • Arachidonic Acid* / blood
  • Arachidonic Acid* / metabolism
  • Child
  • Chloride Channel Agonists / administration & dosage
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Cystic Fibrosis* / immunology
  • Cystic Fibrosis* / metabolism
  • Drug Monitoring / methods
  • Fatty Acids, Monounsaturated* / blood
  • Fatty Acids, Monounsaturated* / metabolism
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Linoleic Acid* / blood
  • Linoleic Acid* / metabolism
  • Lipid Metabolism / drug effects*
  • Male
  • Mutation
  • Pilot Projects
  • Prostaglandins E / metabolism*
  • Prostaglandins E / urine
  • Quinolones / administration & dosage*


  • Aminophenols
  • Chloride Channel Agonists
  • Fatty Acids, Monounsaturated
  • Inflammation Mediators
  • Prostaglandins E
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor
  • palmitoleic acid
  • Arachidonic Acid
  • Linoleic Acid