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A strategy for designing voriconazole dosage regimens to prevent invasive pulmonary aspergillosis based on a cellular pharmacokinetics/pharmacodynamics model

Overview of attention for article published in Journal of Translational Medicine, June 2018
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Title
A strategy for designing voriconazole dosage regimens to prevent invasive pulmonary aspergillosis based on a cellular pharmacokinetics/pharmacodynamics model
Published in
Journal of Translational Medicine, June 2018
DOI 10.1186/s12967-018-1533-4
Pubmed ID
Authors

Taotao Wang, Tao Zhang, Ti Meng, Ying Li, Lu Chen, Qianting Yang, Haiyan Dong, Jin’e Lei, Limei Chen, Yalin Dong

Abstract

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in immunosuppressed patients. Voriconazole is commonly used to prevent and treat IPA in the clinic, but the optimal prophylactic antifungal regimen is unknown. The objective of this study was to clarify the mechanism underlying how voriconazole prevents IPA based on a target cellular pharmacokinetics/pharmacodynamics model, with the aim of identifying a way to design an optimal prophylactic antifungal regimen. A nystatin assay was used to establish a target-cells model for A. fumigatus infection. An inhibitory effect sigmoid Emax model was developed to explore the cellular PK/PD breakpoint, and Monte Carlo simulation was used to design the prophylactic antifungal regimen. The intracellular activity of voriconazole in the target cells varied with its concentration, with the minimum inhibitory concentration (MIC) being an important determinant. For A. fumigatus strains AF293 and AF26, voriconazole decreased the intracellular inoculum by 0.79 and 0.84 lg cfu, respectively. The inhibitory effect sigmoid Emax model showed that 84.01% of the intracellular inoculum was suppressed by voriconazole within 24 h, and that a PK/PD value of 35.53 for the extracellular voriconazole concentration divided by MIC was associated with a 50% suppression of intracellular A. fumigatus. The Monte Carlo simulation results showed that the oral administration of at least 200 mg of voriconazole twice daily was yielded estimated the cumulative fraction of response value of 91.48%. Concentration of voriconazole in the pulmonary epithelial lining fluid and the plasma of > 17.77 and > 1.55 mg/L, respectively, would ensure the PK/PD > 35.53 for voriconazole against most isolates of A. fumigatus and may will be benefit to prevent IPA in clinical applications. This study used a target cellular pharmacokinetics/pharmacodynamics model to reveal a potential mechanism underlying how voriconazole prevents IPA and has provided a method for designing voriconazole prophylactic antifungal regimen in immunosuppressed patients.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 29%
Student > Master 2 14%
Student > Doctoral Student 2 14%
Professor 1 7%
Unknown 5 36%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 36%
Medicine and Dentistry 2 14%
Computer Science 1 7%
Nursing and Health Professions 1 7%
Unknown 5 36%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 June 2019.
All research outputs
#11,645,171
of 15,251,478 outputs
Outputs from Journal of Translational Medicine
#2,220
of 2,879 outputs
Outputs of similar age
#192,171
of 278,690 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 15,251,478 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,879 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
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