DISCREPANCIES IN BIOASSAY AND CHROMATOGRAPHY DETERMINATIONS EXPLAINEDBY METABOLISM OF ITRACONAZOLE TO HYDROXYITRACONAZOLE - STUDIES OF INTERPATIENT VARIATIONS IN CONCENTRATIONS

Pharmacologic studies of itraconazole (IZ), a triazole antifungal, ind icated unexplained differences between bioassay and chromatographic de terminations and large variations in steady-state blood concentrations . We show that concentrations of a hydroxylated metabolite, hydroxyitr aconazole (HIZ), are approximately twofold higher than IZ over a range of concentrations. Though HIZ and IZ appear equipotent against select ed pathogens, HIZ is two to three times more active against a commonly used bioassay fungus but minimally affects IZ activity. Hence, HIZ pr obably contributes importantly to the therapeutic activity attributed to IZ and contributes approximately four to six times the activity of IZ in bioassays, explaining discrepancies observed between assay metho ds.