Unbound Fraction of Clozapine Significantly Decreases with Elevated Plasma Concentrations of the Inflammatory Acute-Phase Protein Alpha-1-Acid Glycoprotein

Background During inflammation, elevated total (unbound plus protein-bound) clozapine plasma concentrations have been observed. Elevated alpha-1-acid glycoprotein concentrations during inflammation are suggested to cause increased plasma clozapine-alpha-1-acid glycoprotein binding, resulting in elevated total clozapine plasma concentrations without significant changes in unbound concentrations. Here, we investigated the association between alpha-1-acid glycoprotein plasma concentrations and clozapine unbound fraction.