ArticleInternational journal of antimicrobial agents2008
A pharmacokinetic/pharmacodynamic mathematical model accurately describes the activity of voriconazole against Candida spp. in vitro.
Article in International journal of antimicrobial agents, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B againstPharmaceutics · 2021Article
- Host-pathogen interactions between the human innate immune system and Candida albicans-understanding and modeling defense and evasion strategies.Frontiers in microbiology · 2015Review
- How fitness reduced, antimicrobial resistant bacteria survive and spread: a multiple pig-multiple bacterial strain model.PloS one · 2014Article
- Evaluation of bactec mycosis IC/F and Plus Aerobic/F blood culture bottles for detection of Candida in the presence of antifungal agents.Journal of clinical microbiology · 2013Article
- Formalizing an integrative, multidisciplinary cancer therapy discovery workflow.Cancer research · 2013Article
- In vitro pharmacokinetic/pharmacodynamic modeling of voriconazole activity against Aspergillus species in a new in vitro dynamic model.Antimicrobial agents and chemotherapy · 2012Article
- Pharmacodynamic modeling of in vitro activity of marbofloxacin against Escherichia coli strains.Antimicrobial agents and chemotherapy · 2011Article
- In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB.Future medicinal chemistry · 2010Review
- A simple in vitro PK/PD model system to determine time-kill curves of drugs against Mycobacteria.Tuberculosis (Edinburgh, Scotland) · 2009Article
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Authors and funding
7 authors.
Funding
Abstract
We developed a pharmacokinetic/pharmacodynamic (PK/PD) mathematical model that fits voriconazole time-kill data against Candida isolates in vitro and used the model to simulate the expected kill curves for typical intravenous and oral dosing regimens. A series of Emax mathematical models were used to fit time-kill data for two isolates each of Candida albicans, Candida glabrata and Candida parapsilosis. PK parameters extracted from human data sets were used in the model to simulate kill curves for each isolate. Time-kill data were best fit by using an adapted sigmoidal Emax model that corrected for delays in candidal growth and the onset of voriconazole activity, saturation of the number of Candida and the steepness of the concentration-response curve. The rates of maximal killing by voriconazole (kmax) were highly correlated with the growth rates (ks) of the isolates (Pearson's correlation coefficient=0.9861). Simulations using PK parameters derived from the human data sets showed fungistatic effects against each of the isolates. In conclusion, we demonstrated that the activity of voriconazole against Candida isolates can be accurately described using a mathematical model. In the future, it might be possible to devise optimal dosing regimens of voriconazole using the model and PK data collected in vivo.
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