Getting antifungal drug levels right – why does it matter?
David Andes MD
University of Wisconsin, Madison, Wisconsin, USA

Antifungal drugs (e.g. Itraconazole, Voricaonazole and Posaconazole) have a variable and unpredictable dose–concentration relationship, and therefore need careful concentration management.  Problems may occur whether the concentration is either too low or too high, and it is difficult to maintain a concentration that falls within the therapeutic window.  

Factors which impact on the concentration of these drugs are the amount given and absorption from the gastrointestinal tract. In the stomach environment, both food and stomach acid may affect the drug’s concentration – Voriconazole, for example, is best absorbed on an empty stomach. 

Antifungal drugs are eliminated via normal liver metabolism, but the liver may metabolise the drugs either too quickly or too slowly.  

Concentration can be managed by measuring antifungal concentration at the start of therapy, after a change in dose, if the patient is getting worse or if the patient feels ill or shows signs of toxicity.

The absorption of the drug, its elimination and the amount given can all be adjusted in order to achieve the desired concentration, e.g. an acidic drink such as cola will improve the absorption of Itraconazole.

With thanks to Fran Stokes