Comment on “Population Pharmacokinetics of Total and Unbound Isavuconazole in Critically Ill Patients: Implications for Adaptive Dosing Strategies” and “High Variability in Isavuconazole Unbound Fraction in Clinical Practice: A Call to Reconsider Pharmacokinetic/Pharmacodynamic Targets and Breakpoints”

Currently, there is no evidence that unbound isavuconazole concentrations are a better predictor of treatment response than total concentrations. [...]clinical implementation of monitoring unbound isavuconazole concentrations in routine clinical practice is difficult to justify. While isavuconazole...

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Published in:Clinical pharmacokinetics Vol. 63; no. 5; pp. 731 - 733
Main Authors: Kong, Leping, Alffenaar, Jan-Willem C., Stocker, Sophie L.
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.05.2024
Springer Nature B.V
Subjects:
Antibiotics
Biomarkers
Biosensors
Clinical medicine
Conflicts of interest
Drug dosages
Internal Medicine
Laboratories
Letter to the Editor
Medicine
Medicine & Public Health
Pharmaceutical industry
Pharmacodynamics
Pharmacokinetics
Pharmacology/Toxicology
Pharmacotherapy
Proteins
Real time
ISSN:0312-5963, 1179-1926, 1179-1926
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Abstract Currently, there is no evidence that unbound isavuconazole concentrations are a better predictor of treatment response than total concentrations. [...]clinical implementation of monitoring unbound isavuconazole concentrations in routine clinical practice is difficult to justify. While isavuconazole is highly protein bound, it has a low intrinsic clearance; therefore, changes in the fraction unbound are unlikely to impact its pharmacokinetics (specifically clearance). [...]we propose that the importance of measuring unbound isavuconazole concentrations, as a better predictor of treatment response, should be established before implementation of routine monitoring of free concentrations. [...]a better understanding of isavuconazole pharmacokinetics/pharmacodynamics and its unbound drug concentrations will have practical implications regarding how we perform therapeutic drug monitoring.
AbstractList Currently, there is no evidence that unbound isavuconazole concentrations are a better predictor of treatment response than total concentrations. [...]clinical implementation of monitoring unbound isavuconazole concentrations in routine clinical practice is difficult to justify. While isavuconazole is highly protein bound, it has a low intrinsic clearance; therefore, changes in the fraction unbound are unlikely to impact its pharmacokinetics (specifically clearance). [...]we propose that the importance of measuring unbound isavuconazole concentrations, as a better predictor of treatment response, should be established before implementation of routine monitoring of free concentrations. [...]a better understanding of isavuconazole pharmacokinetics/pharmacodynamics and its unbound drug concentrations will have practical implications regarding how we perform therapeutic drug monitoring.
Author Alffenaar, Jan-Willem C.
Stocker, Sophie L.
Kong, Leping
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  givenname: Sophie L.
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  surname: Stocker
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  organization: Faculty of Medicine and Health, School of Pharmacy, University of Sydney, The University of Sydney Infectious Disease Institute, Department of Pharmacy, Westmead Hospital, Department of Clinical Pharmacology & Toxicology, St. Vincent’s Hospital
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10.1128/mSphere.00098-17
10.1007/s40262-023-01311-w
10.1128/msphere.00274-17
10.1007/s40262-023-01305-8
10.1097/ftd.0000000000000632
10.3390/antibiotics12101478
10.1007/s40262-012-0018-5
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SubjectTerms Antibiotics
Biomarkers
Biosensors
Clinical medicine
Conflicts of interest
Drug dosages
Internal Medicine
Laboratories
Letter to the Editor
Medicine
Medicine & Public Health
Pharmaceutical industry
Pharmacodynamics
Pharmacokinetics
Pharmacology/Toxicology
Pharmacotherapy
Proteins
Real time
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