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Computational pharmacokinetics/pharmacodynamics of rifampin in a mouse tuberculosis infection model

Overview of attention for article published in Journal of Pharmacokinetics and Pharmacodynamics, May 2015
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  • Good Attention Score compared to outputs of the same age (70th percentile)

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Title
Computational pharmacokinetics/pharmacodynamics of rifampin in a mouse tuberculosis infection model
Published in
Journal of Pharmacokinetics and Pharmacodynamics, May 2015
DOI 10.1007/s10928-015-9419-z
Pubmed ID
Authors

Michael A. Lyons, Anne J. Lenaerts

Abstract

One critical approach to preclinical evaluation of anti-tuberculosis (anti-TB) drugs is the study of correlations between drug exposure and efficacy in animal TB infection models. While such pharmacokinetic/pharmacodynamic (PK/PD) studies are useful for the identification of optimal clinical dosing regimens, they are resource intensive and are not routinely performed. A mathematical model capable of simulating the PK/PD properties of drug therapy for experimental TB offers a way to mitigate some of the practical obstacles to determining the PK/PD index that best correlates with efficacy. Here, we present a preliminary physiologically based PK/PD model of rifampin therapy in a mouse TB infection model. The computational framework integrates whole-body rifampin PKs, cell population dynamics for the host immune response to Mycobacterium tuberculosis infection, drug-bacteria interactions, and a Bayesian method for parameter estimation. As an initial application, we calibrated the model to a set of available rifampin PK/PD data and simulated a separate dose fractionation experiment for bacterial killing kinetics in the lungs of TB-infected mice. The simulation results qualitatively agreed with the experimentally observed PK/PD correlations, including the identification of area under the concentration-time curve as best correlating with efficacy. This single-drug framework is aimed toward extension to multiple anti-TB drugs in order to facilitate development of optimal combination regimens.

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X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 2%
Unknown 50 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 31%
Researcher 9 18%
Student > Doctoral Student 5 10%
Student > Master 4 8%
Student > Bachelor 2 4%
Other 3 6%
Unknown 12 24%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 10 20%
Agricultural and Biological Sciences 7 14%
Medicine and Dentistry 6 12%
Biochemistry, Genetics and Molecular Biology 4 8%
Mathematics 2 4%
Other 8 16%
Unknown 14 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 10 June 2015.
All research outputs
#7,336,515
of 25,374,917 outputs
Outputs from Journal of Pharmacokinetics and Pharmacodynamics
#105
of 477 outputs
Outputs of similar age
#81,616
of 281,298 outputs
Outputs of similar age from Journal of Pharmacokinetics and Pharmacodynamics
#2
of 3 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 477 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,298 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.