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Updated: Jul 4, 2025

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 Population Pharmacokinetics in Pediatric Patients with Cystic Fibrosis: A First Step Toward

Naïm Bouazza1,2,3, Saïk Urien4,5,6, Frantz Foissac4,5,6

  • 1Université Paris Cité, EA7323, Paris, France. naim.bouazza@aphp.fr.

Clinical Pharmacokinetics
|February 4, 2024
PubMed

Insights

This study analyzed lumacaftor/ivacaftor pharmacokinetics in children with cystic fibrosis (CF). Bodyweight and liver function impact drug levels, suggesting dose adjustments are needed for optimal CFTR modulator therapy.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Cystic Fibrosis Research

Background:

  • Cystic Fibrosis (CF) treatment has advanced with CFTR modulators.
  • The lumacaftor/ivacaftor combination is approved for CF patients over six years old.
  • Pharmacokinetic (PK) studies in pediatric populations are vital for optimizing lumacaftor/ivacaftor therapy.

Purpose of the Study:

  • To characterize the population PK (PPK) of lumacaftor and ivacaftor in pediatric CF patients.
  • To identify factors contributing to interindividual variability in drug exposure.
  • To explore the relationship between drug exposure and clinical outcomes.

Main Methods:

  • Population PK analysis of 75 children with CF using Monolix software.
  • Analysis included lumacaftor, ivacaftor, and their metabolites (ivacaftor-M1, ivacaftor-M6).
  • Investigated associations between patient characteristics and drug concentrations.

Main Results:

  • Significant interindividual variability in lumacaftor/ivacaftor exposure was observed.
  • Patient bodyweight and hepatic function (AST) were identified as key factors influencing variability.
  • Increased exposure to ivacaftor after 48 weeks correlated with improved FEV1.

Conclusions:

  • This is the first PPK analysis of lumacaftor/ivacaftor in pediatric CF patients.
  • Dose adjustments based on identified variability factors are recommended to enhance treatment efficacy.
  • Therapeutic drug monitoring could be beneficial for optimizing lumacaftor/ivacaftor dosing in children with CF.
Abstract

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