Antifungal pharmacokinetics and pharmacodynamics.
Successful treatment of infectious diseases requires choice of the most suitable antimicrobial agent, comprising consideration of drug pharmacokinetics (PK), including penetration into infection site, pathogen susceptibility, optimal route of drug administration, drug dose, frequency of administration, duration of therapy, and drug toxicity. Antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) studies consider these variables and have been useful in drug development, optimizing dosing regimens, determining susceptibility breakpoints, and limiting toxicity of antifungal therapy. Here the concepts of antifungal PK/PD studies are reviewed, with emphasis on methodology and application. The initial sections of this review focus on principles and methodology. Then the pharmacodynamics of each major antifungal drug class (polyenes, flucytosine, azoles, and echinocandins) is discussed. Finally, the review discusses novel areas of pharmacodynamic investigation in the study and application of combination therapy.
University of Wisconsin, Madison, Wisconsin 53705.
Alexander J
AJ
Lepak
University of Wisconsin, Madison, Wisconsin 53705.
David R
DR
Andes
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004195:Disease Models, Animal; D054714:Echinocandins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D005437:Flucytosine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009181:Mycoses / Q000188:drug therapy*; D011090:Polyenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D000935:Antifungal Agents; D054714:Echinocandins; D011090:Polyenes; D014230:Triazoles; D005437:Flucytosine