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Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study

Overview of attention for article published in Critical Care, December 2015
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  • Above-average Attention Score compared to outputs of the same age and source (53rd percentile)

Mentioned by

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6 tweeters

Citations

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140 Dimensions

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94 Mendeley
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Title
Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study
Published in
Critical Care, December 2015
DOI 10.1186/s13054-015-0891-z
Pubmed ID
Authors

Kiran Shekar, Jason A Roberts, Charles I Mcdonald, Sussan Ghassabian, Chris Anstey, Steven C Wallis, Daniel V Mullany, Yoke L Fung, John F Fraser

Abstract

Vital drugs may be degraded or sequestered in extracorporeal membrane oxygenation (ECMO) circuits with lipophilic drugs considered to be particularly vulnerable. However, the circuit effects on protein bound drugs have not been fully elucidated. This experiment aimed to investigate the influence of plasma protein binding on drug disposition in ex vivo ECMO circuits. Four identical ECMO circuits comprising centrifugal pumps and polymethyl pentene oxygenators and were utilised. The circuits were primed with crystalloid, albumin and fresh human whole blood and maintained at a physiological pH and temperature for 24 hours. After baseline sampling, known quantities of study drugs (ceftriaxone, ciprofloxacin, linezolid, fluconazole, caspofungin and thiopentone) were injected into the circuit to achieve therapeutic concentrations. Equivalent doses of these drugs were also injected into four polypropylene jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the controls and the ECMO circuits over 24 hours and the concentrations of the study drugs were quantified using validated chromatographic assays. A regression model was constructed to examine the relationship between circuit drug recovery as the dependent variable and protein binding and partition coefficient (measure of lipophilicity) as explanatory variables. Four hundred and eighty samples were analysed. There was no significant loss of any study drugs in the controls over 24 hours. The average drug recoveries from the ECMO circuits at 24 hours respectively were ciprofloxacin 96%, linezolid 91%, fluconazole 91%, ceftriaxone 80%, caspofungin 56% and thiopentone 12%. There was a significant reduction of ceftriaxone (p = 0.01), caspofungin (p = 0.01) and thiopentone (p = 0.008) concentrations in the ECMO circuit at 24 hours. Both protein binding and partition coefficient were highly significant with the model possessing a high coefficient of determination (R(2) = 0.88, p < 0.001). Recovery of the highly protein bound drugs ceftriaxone, caspofungin and thiopentone were significantly lower in the ECMO circuits at 24 hours. For drugs with similar lipophilicity, the extent of protein binding may determine circuit drug loss. Future clinical population pharmacokinetic studies should initially focus on drugs with greater lipophilicity and protein binding and therapeutic drug monitoring should be strongly considered for such drugs.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 94 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 1%
France 1 1%
Brazil 1 1%
Unknown 91 97%

Demographic breakdown

Readers by professional status Count As %
Other 16 17%
Student > Ph. D. Student 13 14%
Researcher 12 13%
Student > Doctoral Student 8 9%
Student > Postgraduate 7 7%
Other 19 20%
Unknown 19 20%
Readers by discipline Count As %
Medicine and Dentistry 36 38%
Pharmacology, Toxicology and Pharmaceutical Science 21 22%
Biochemistry, Genetics and Molecular Biology 3 3%
Engineering 3 3%
Nursing and Health Professions 2 2%
Other 7 7%
Unknown 22 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 14 April 2015.
All research outputs
#3,743,407
of 12,786,839 outputs
Outputs from Critical Care
#2,436
of 4,101 outputs
Outputs of similar age
#69,649
of 223,855 outputs
Outputs of similar age from Critical Care
#25
of 65 outputs
Altmetric has tracked 12,786,839 research outputs across all sources so far. This one is in the 49th percentile – i.e., 49% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,101 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 35th percentile – i.e., 35% of its peers scored the same or lower than it.
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 223,855 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 65% of its contemporaries.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.