ArticleAntimicrobial agents and chemotherapy2012
Pharmacodynamic effects of simulated standard doses of antifungal drugs against Aspergillus species in a new in vitro pharmacokinetic/pharmacodynamic model.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
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- A new PK/PD target for assessing efficacy of micafungin against Candida parapsilosis.The Journal of antimicrobial chemotherapy · 2024Article
- Development of an in vitro pharmacokinetic/pharmacodynamic model in the presence of serum for studying micafungin activity against Candida albicans: a need for revision of CLSI susceptibility breakpoints.The Journal of antimicrobial chemotherapy · 2023Article
- Assessment of Antifungal Pharmacodynamics.Journal of fungi (Basel, Switzerland) · 2023Article
- The Application of Hollow Fiber Cartridge in Biomedicine.Pharmaceutics · 2022Review
- Pharmacodynamic Parameters of Pharmacokinetic/Pharmacodynamic (PK/PD) Integration Models.Frontiers in veterinary science · 2022Review
- The Role of New Posaconazole Formulations in the Treatment of Candida albicans Infections: Data from anAntimicrobial agents and chemotherapy · 2021Article
- Modeling Invasive Aspergillosis: How Close Are Predicted Antifungal Targets?Journal of fungi (Basel, Switzerland) · 2020Review
- Toward Harmonization of Voriconazole CLSI and EUCAST Breakpoints for Candida albicans Using a ValidatedAntimicrobial agents and chemotherapy · 2020Article
- Pharmacokinetic/Pharmacodynamic Integration of Doxycycline AgainstFrontiers in pharmacology · 2019Article
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- A New Marker of Echinocandin Activity in anAntimicrobial agents and chemotherapy · 2018Article
- The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin againstOncotarget · 2018Article
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- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Prognostic value of galactomannan: current evidence for monitoring response to antifungal therapy in patients with invasive aspergillosis.Journal of pharmacokinetics and pharmacodynamics · 2017Review
- The PK/PD Interactions of Doxycycline against Mycoplasma gallisepticum.Frontiers in microbiology · 2016Article
- Optimization of polyene-azole combination therapy against aspergillosis using an in vitro pharmacokinetic-pharmacodynamic model.Antimicrobial agents and chemotherapy · 2015Article
- Susceptibility breakpoints for amphotericin B and Aspergillus species in an in vitro pharmacokinetic-pharmacodynamic model simulating free-drug concentrations in human serum.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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