High Variability in Isavuconazole Unbound Fraction in Clinical Practice: A Call to Reconsider Pharmacokinetic/Pharmacodynamic Targets and Breakpoints

Abstract

Isavuconazole exposure–response relationships have been studied with a focus on total rather than unbound exposure, assuming a constant unbound fraction of 1%. We observed a median (range) unbound fraction of 1.59% (0.42–5.30%) in patients. This highly variable protein binding asks for re-evaluation of current pharmacokinetic and pharmacodynamic targets for isavuconazole.