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Updated: Apr 26, 2026

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
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Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Published on: October 15, 2017

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Lumacaftor-Ivacaftor in Pediatric Patients With Cystic Fibrosis and Advanced Liver Disease: A Pilot Study

Adeline Y L Lim1, Maria P Hernández-Mitre2, Peter J Lewindon3

  • 1Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, Queensland, Australia; University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia.

Clinical Therapeutics
|April 24, 2026
PubMed

Insights

Lumacaftor-ivacaftor (LI) pharmacokinetics in advanced cystic fibrosis-related liver disease (ACFRLD) showed altered drug concentrations. This suggests potential absorption and excretion issues, highlighting the need for individualized treatment in this population.

Area of Science:

  • Pharmacology
  • Hepatology
  • Pediatric Medicine

Background:

  • Lumacaftor-ivacaftor (LI) is a CFTR modulator for cystic fibrosis (CF) patients with the F508del-CFTR variant.
  • Use of LI in advanced cystic fibrosis-related liver disease (ACFRLD) is cautioned due to potential liver impairment.
  • Benefits for nutrition and lung function may exist despite liver concerns.

Purpose of the Study:

  • To describe the pharmacokinetics of LI and its metabolites (ivacaftor-M1 and ivacaftor-M6) in pediatric patients with ACFRLD.
  • To assess the safety and tolerability of LI in this specific patient group.

Main Methods:

  • A pilot study involving three pediatric patients with ACFRLD.
  • Patients received a 4-week regimen of half-dose then full-dose LI.
  • Weekly liver function monitoring and pharmacokinetic sampling were performed. Stool samples were collected for comparison with a control group.

Main Results:

  • Liver function remained stable in patients with ACFRLD.
  • One patient experienced transient hyperammonemia, resolving upon LI cessation.
  • Plasma concentrations of ivacaftor and lumacaftor were decreased, while M1 and M6 metabolites were elevated compared to controls.

Conclusions:

  • Findings suggest reduced ivacaftor absorption and impaired biliary excretion in ACFRLD.
  • Elevated M1, M6, and decreased lumacaftor concentrations were observed.
  • Pharmacokinetic variability indicates a potential role for individualized profiling in CFTR modulator therapy for ACFRLD.
Abstract

Keywords:
Advanced cystic fibrosis–related liver diseaseCystic fibrosisIvacaftorLumacaftorOrkambiPharmacokinetics

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