Antifungal serum concentration monitoring: an update

• Published in: Journal of antimicrobial chemotherapy 2008-01, Vol.61 (1), p.17-25
• Main Authors: Goodwin, Megan L., Drew, Richard H.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - adverse effects; Antifungal Agents - blood; Antifungal Agents - pharmacokinetics; Antifungal Agents - therapeutic use; Aspergillus; azoles; Azoles - adverse effects; Azoles - blood; Azoles - pharmacokinetics; Azoles - therapeutic use; Biological and medical sciences; Blood tests; Echinocandins - adverse effects; Echinocandins - blood; Echinocandins - pharmacokinetics; Echinocandins - therapeutic use; Flucytosine - adverse effects; Flucytosine - blood; Flucytosine - pharmacokinetics; Flucytosine - therapeutic use; Fungal infections; Humans; Kinetics; Medical sciences; Microbiology; Monitoring, Physiologic; Mycoses - blood; Mycoses - drug therapy; Patient safety; pharmacodynamics; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Risk factors; Toxicity
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkm389

Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole).