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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
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Characterization of isavuconazole pharmacokinetics and pharmacodynamics in a real-life cohort

Monia Guidi1,2,3, Jade Couchepin4, Ilana Reinhold5,6

  • 1Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Jac-Antimicrobial Resistance
|May 6, 2026
PubMed
Abstract

Insights

Therapeutic drug monitoring (TDM) for isavuconazole (ISA) may be beneficial. Real-world data show ISA exposure variability correlates with treatment outcomes, suggesting TDM can optimize patient management and target achievement.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Infectious Diseases

Background:

  • Isavuconazole (ISA) is a crucial antifungal for invasive aspergillosis and mucormycosis.
  • Therapeutic drug monitoring (TDM) for ISA is infrequently performed due to perceived low variability and lack of defined thresholds.
  • Real-world characterization of ISA pharmacokinetics and pharmacodynamics is needed.

Purpose of the Study:

  • To characterize isavuconazole (ISA) pharmacokinetics and pharmacodynamics in clinical practice.
  • To assess the potential utility of therapeutic drug monitoring (TDM) for ISA.
  • To explore exposure-response relationships for ISA treatment outcomes and toxicity.

Main Methods:

  • Developed and validated a population pharmacokinetic (popPK) model for ISA using patient data from three Swiss hospitals.
  • Conducted exploratory pharmacokinetic-pharmacodynamic analyses correlating ISA concentrations (trough and AUC) with outcomes and hepatotoxicity.
  • Utilized model-based simulations to evaluate the role of TDM in patient management.

Main Results:

  • A one-compartment popPK model with interindividual variability in clearance best described ISA concentrations.
  • Body mass index was the only covariate significantly impacting ISA volume of distribution.
  • Exposure-response analyses indicated a trend between ISA exposure and treatment success, but not toxicity.
  • Simulations suggested TDM could improve the proportion of patients achieving target ISA exposure ranges.

Conclusions:

  • Isavuconazole (ISA) exposure exhibits significant interindividual variability in real-world settings.
  • ISA exposure appears to correlate with treatment outcomes, supporting its clinical relevance.
  • Therapeutic drug monitoring (TDM) may play a beneficial role in optimizing ISA dosing and achieving target exposures for improved patient management.

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