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Itraconazole is a synthetic triazole antifungal drug approved for treatment and prophylaxis of a variety of fungal infections. Its activity results from inhibition of fungal synthesis of ergosterol, an integral component of fungal cell membranes.
Concerns about adequate absorption and drug interactions are some of the major indications for therapeutic drug monitoring. Mean oral bioavailability approximates 55% but is highly variable; absorption can be enhanced by food or acidic drinks. Hepatic enzyme inducers can cause low serum itraconazole levels, and coadministration of these drugs has been associated with itraconazole therapeutic failure.
Itraconazole therapeutic efficacy is greatest when serum concentrations exceed 0.5 mcg/mL for localized infections, or 1.0 mcg/mL for systemic infections. An active metabolite, hydroxyitraconazole, is present in serum at roughly twice the level of the parent drug. These concentrations refer to analysis by HPLC; quantitation by bioassay results in considerably higher apparent drug measurements, due to reactivity with the active metabolite.
Verifying systemic absorption of orally administered itraconazole
The test is indicated in patients with life-threatening fungal infections and in patients considered at risk for poor absorption or rapid clearance of itraconazole.
A lower cutoff concentration has not been defined that applies in all cases. The serum concentration must be interpreted in association with other variables, such as the nature of the infection, the specific microorganism, and minimal inhibitory concentration (MIC) results, if available. Localized infections are more likely to respond when serum itraconazole is >0.5 mcg/mL (by HPLC); systemic infections generally require drug concentrations >1.0 mcg/mL.
Enteropathy, H2-histamine receptor blockers, hepatic enzyme inducers, and other variables can result in low to nondetectable serum levels with concomitant high risk of therapeutic failure.
AIDS patients and organ transplant patients receiving immunosuppressive therapy tend to have lower serum itraconazole levels on standard doses and are thus at high risk of therapeutic failure.
>0.5 mcg/mL (localized infection)
>1 mcg/mL (systemic infection)
No therapeutic range established; activity and serum concentration are similar to parent drug.
1. Andes D, Pascual A, Marchetti O: Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009;53(1):24-34
2. Hope WW, Billaud EM, Lestner J, Denning DW: Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis 2008;21:580-586