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Population pharmacokinetics of isavuconazole in hematologic patients: implications for model-informed precision

Diego Peña-Lorenzo1, José Germán Sánchez-Hernández2, Irene Conde-González3

  • 1Pharmacy Service, University Hospital of Salamanca, Spain; Biomedical Research Institute of Salamanca (IBSAL), Spain.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|June 9, 2025
PubMed
Abstract

Insights

Body surface area and serum albumin impact isavuconazole clearance in hematologic patients. This population pharmacokinetic model supports precision dosing for invasive fungal infections (IFIs).

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Pharmacometrics

Background:

  • Isavuconazole is a broad-spectrum antifungal for invasive fungal infections (IFIs).
  • Hematologic patients may experience altered isavuconazole pharmacokinetics due to clinical factors.
  • Precision dosing is crucial for optimizing drug exposure in this population.

Purpose of the Study:

  • Develop a population pharmacokinetic (popPK) model for isavuconazole in adult hematologic patients.
  • Identify factors influencing isavuconazole drug exposure.
  • Support model-informed precision dosing strategies.

Main Methods:

  • Prospective study with therapeutic drug monitoring (TDM) in adult hematologic patients.
  • Isavuconazole plasma concentrations quantified using UPLC-UV.
  • Population pharmacokinetic modeling performed using NONMEM v.7.5.0.

Main Results:

  • A one-compartment model with first-order absorption and elimination adequately described the data.
  • Body surface area (BSA) and serum albumin (ALB) significantly impacted isavuconazole clearance.
  • The developed popPK model demonstrated good precision, robustness, and predictive performance.

Conclusions:

  • BSA and serum ALB are key covariates affecting isavuconazole clearance in hematologic patients.
  • The popPK model supports individualized isavuconazole dosing.
  • Further research is needed to refine absorption characterization and dosage recommendations.
Keywords:
Hematologic patients;, Population pharmacokineticsIsavuconazoleModel-informed precision dosing

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