The Impact of Pharmacodynamics on antifungal Treatment.

ARNOLD LOUIE, MD

Author address: 

Ordway Research Institute, Albany, NY.

Abstract: 

The morbidity and mortality of invasive fungal infections remains a significant problem.The goal of this symposium is to show how pharmacodynamic (PD) principles can be used in conjunction with mathematical models (MM) to develop logical, thoughtful antifungal drug dosage and dosing strategies to optimize treatment outcome. A review of PD principles and mathematical modeling, as it applies to PD studies, will be presented. Subsequently, a discussion of the following topics will be provided. 1. Focusing on azole drugs, instruction will be provided on how the application of PD principles and the concept of ``human equivalent exposures'' (HEE) can be used to assess the relative strength with which in-vitro and animal infection model data that is reported in the literature may be applied to the clinic. 2. Using fluconazole and voriconazole as examples, a discussion will be provided on how PD and MM approaches may be used to provide dose target support for investigational and established antifungal drugs. 3. A paradigm will be discussed for using PD, MM and HEE to design animal infection models that may be used to develop novel treatment regimens for pathogens for which standard treatment regimens have failed or do not exist. 4. Instruction will be provided on how PD and MM principles have been used to validate the NCCLS breakpoints for fluconazole for the treatment of invasive candidal disease. 5. A review of how PD and MM principles may be used to unify the discrepancies that may exist between in-vitro, in-vivo, and human studies of antifungal combination therapy and 6. A discussion on how animal PD studies have provided insight on novel dosing strategies that hold promise in decreasing drug toxicity without compromising drug efficacy. New areas of application of PD and MM principles will be highlighted, including the potential use of these methods: to prevent emergence of antifungal resistance during therapy, to optimize the use of cytokines (i.e.,: interferon) as an adjunct to standard antifungal agents, and the importance of identifying the persistent of drug in tissues as a means of understanding drug efficacy and in improving study design.
2003

abstract No: 

634

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd