Antifungal Pharmacokinetics and Pharmacodynamics

Abstract

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. PHARMACOKINETICS

Benzothiourea Derivatives Target the Secretory Pathway of the Human Fungal Pathogen Cryptococcus neoformans

“…While initial in vivo studies did not show a reduction in brain burden, the levels in the serum reach 2 μg/mL, just at the level of MIC, and do not maintain concentrations at or above MIC for very long. Typically, C max or AUC in serum or tissue needs to be well over MIC or the serum/tissue concentration needs to maintain a concentration over MIC for a prolonged period of time for molecules to have in vivo efficacy . However, the ability to readily penetrate the BBB and enter the brain tissue is a very desirable characteristic.…”

“…Typically, C max or AUC in serum or tissue needs to be well over MIC or the serum/tissue concentration needs to maintain a concentration over MIC for a prolonged period of time for molecules to have in vivo efficacy. 45 However, the ability to readily penetrate the BBB and enter the brain tissue is a very desirable characteristic. The majority of small molecules (98%) do not cross the BBB.…”