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• W2012172825 abstract "ABSTRACT In conventional ΜΙC tests, fungi are exposed to constant drug concentrations, whereas in vivo , fungi are exposed to changing drug concentrations. Therefore, we developed a new in vitro pharmacokinetic/pharmacodynamic model where human plasma pharmacokinetics of standard doses of 1 mg/kg amphotericin B, 4 mg/kg voriconazole, and 1 mg/kg caspofungin were simulated and their pharmacodynamic characteristics were determined against three clinical isolates of Aspergillus fumigatus , Aspergillus flavus , and Aspergillus terreus with identical MICs (1 mg/liter for amphotericin B, 0.5 mg/liter for voriconazole) and minimum effective concentrations (0.5 mg/liter for caspofungin). This new model consists of an internal compartment (a 10-ml dialysis tube made out of a semipermeable cellulose membrane allowing the free diffusion of antifungals but not galactomannan) inoculated with Aspergillus conidia and placed inside an external compartment (a 700-ml glass beaker) whose content is diluted after the addition of antifungal drugs by a peristaltic pump at the same rate as the clearance of the antifungal drugs in human plasma. Fungal growth was assessed by galactomannan production. Despite demonstrating the same MICs, amphotericin B completely inhibited (100%) A. fumigatus but not A. flavus and A. terreus , whose growth was delayed for 7.53 and 22.8 h, respectively. Voriconazole partially inhibited A. fumigatus (49.5%) and Α. flavus (27.9%) but not Α. terreus ; it delayed their growth by 3.99 h ( A. fumigatus ) and 5.37 h (Α. terreus ). Caspofungin did not alter galactomannan production in all of the species but A. terreus . The new model simulated human pharmacokinetics of antifungal drugs and revealed important pharmacodynamic differences in their activity." @default.
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• W2012172825 date "2012-01-01" @default.
• W2012172825 modified "2023-10-16" @default.
• W2012172825 title "Pharmacodynamic Effects of Simulated Standard Doses of Antifungal Drugs against Aspergillus Species in a New <i>In Vitro</i> Pharmacokinetic/Pharmacodynamic Model" @default.
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• W2012172825 doi "https://doi.org/10.1128/aac.00662-11" @default.
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