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Inflammation down-regulates CYP3A4-catalysed drug metabolism in hemodialysis patients

Overview of attention for article published in BMC Pharmacology and Toxicology, June 2018
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Title
Inflammation down-regulates CYP3A4-catalysed drug metabolism in hemodialysis patients
Published in
BMC Pharmacology and Toxicology, June 2018
DOI 10.1186/s40360-018-0221-6
Pubmed ID
Authors

Hadi Molanaei, Abdul Rashid Qureshi, Olof Heimbürger, Bengt Lindholm, Ulf Diczfalusy, Björn Anderstam, Leif Bertilsson, Peter Stenvinkel

Abstract

Recent studies indicate that inflammation may also affect CYP3A4 activity. Associations of CYP3A4-mediated metabolism of quinine, with inflammatory biomarkers were investigated in patients undergoing maintenance hemodialysis (HD). A single dose of 100 mg quinine was given to 44 HD patients and the plasma concentration of quinine and its metabolite 3-OH-quinine were measured 12 h after drug intake. The ratios of quinine/3-OH-quinine and 4β-OH-cholesterol/cholesterol were used as markers of CYP3A4 activity. Inflammatory biomarkers, high-sensitive CRP (hsCRP), pentraxin 3 (PTX3) and orosomucoid were followed during 4 weeks prior to quinine administration. The quinine/3-OH-quinine ratio correlated with median concentrations of hsCRP (Rho = 0.48; p = 0.001) and orosomucoid (Rho = 0.44; p = 0.003), and also with interleukin-6 at 12 h after drug intake (Rho = 0.43; P = 0.004) but not PTX3. In multivariate regression analysis, the correlation between CYP3A4 activity and median hsCRP remained borderline significant (p = 0.05). 4β-OH-cholesterol/cholesterol ratio correlated with quinine/3-OH-quinine (p = 0.008), but not with any of the inflammation markers. The association between CYP3A4 activity and inflammatory biomarkers suggest that the activity of CYP3A4 is reduced by inflammation in HD patients. Further studies are needed to confirm this finding and to assess to what extent magnitude and duration of inflammation as well as the microbiota affect drug metabolism.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Student > Bachelor 5 18%
Student > Master 3 11%
Professor 1 4%
Lecturer > Senior Lecturer 1 4%
Other 2 7%
Unknown 10 36%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 18%
Medicine and Dentistry 4 14%
Nursing and Health Professions 2 7%
Engineering 2 7%
Psychology 1 4%
Other 3 11%
Unknown 11 39%
Attention Score in Context

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 26 March 2019.
All research outputs
#18,640,437
of 23,092,602 outputs
Outputs from BMC Pharmacology and Toxicology
#314
of 445 outputs
Outputs of similar age
#254,161
of 328,981 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#11
of 15 outputs
Altmetric has tracked 23,092,602 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 445 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one is in the 17th percentile – i.e., 17% 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 328,981 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.