In Vivo Pharmacodynamics of Antifungal Drugs in Treatment of Candidiasis

The field of antimicrobial pharmacodynamics examines the relationship between drug pharmacokinetics and antimicrobial activity or host toxicity (9). These investigations have been valuable for defining optimal antimicrobial dosing regimens and validating in vitro susceptibility breakpoints (4, 14, 25). The concepts encompassing this discipline were defined initially with antibacterial compounds (9, 34, 35). With the advent of standardized and reproducible antifungal susceptibility testing, similar pharmacodynamic analyses have been undertaken (24). Both in vitro and in vivo models have been able to demonstrate a correlation between drug dose, the MIC for an organism, and outcome (15, 17, 18, 36, 37). These investigations have been important for describing the relative potencies of antifungal drugs against a number of important pathogens. More recent in vivo pharmacodynamic investigations have examined the relationship among drug dose, dosing interval, MIC, and treatment outcome to define the specific pharmacodynamic parameter and parameter magnitude predictive of antifungal drug activity. This minireview summarizes these in vivo antifungal pharmacodynamic investigations.