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Pre-clinical evaluation of CYP 2D6 dependent drug–drug interactions between primaquine and SSRI/SNRI antidepressants

Overview of attention for article published in Malaria Journal, May 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

Mentioned by

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1 news outlet
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4 X users

Citations

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15 Dimensions

Readers on

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33 Mendeley
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Title
Pre-clinical evaluation of CYP 2D6 dependent drug–drug interactions between primaquine and SSRI/SNRI antidepressants
Published in
Malaria Journal, May 2016
DOI 10.1186/s12936-016-1329-z
Pubmed ID
Authors

Xiannu Jin, Brittney Potter, Thu-lan Luong, Jennifer Nelson, Chau Vuong, Corttney Potter, Lisa Xie, Jing Zhang, Ping Zhang, Jason Sousa, Qigui Li, Brandon S. Pybus, Mara Kreishman-Deitrick, Mark Hickman, Philip L. Smith, Robert Paris, Gregory Reichard, Sean R. Marcsisin

Abstract

The liver-stage anti-malarial activity of primaquine and other 8-aminoquinoline molecules has been linked to bio-activation through CYP 2D6 metabolism. Factors such as CYP 2D6 poor metabolizer status and/or co-administration of drugs that inhibit/interact with CYP 2D6 could alter the pharmacological properties of primaquine. In the present study, the inhibitory potential of the selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitor (SNRI) classes of antidepressants for CYP 2D6-mediated primaquine metabolism was assessed using in vitro drug metabolism and in vivo pharmacological assays. The SSRI/SNRI classes of drug displayed a range of inhibitory activities on CYP 2D6-mediated metabolism of primaquine in vitro (IC50 1-94 μM). Fluoxetine and paroxetine were the most potent inhibitors (IC50 ~1 µM) of CYP 2D6-mediated primaquine metabolism, while desvenlafaxine was the least potent (IC50 ~94 µM). The most potent CYP 2D6 inhibitor, fluoxetine, was chosen to investigate the potential pharmacological consequences of co-administration with primaquine in vivo. The pharmacokinetics of a CYP 2D6-dependent primaquine metabolite were altered upon co-administration with fluoxetine. Additionally, in a mouse malaria model, co-administration of fluoxetine with primaquine reduced primaquine anti-malarial efficacy. These results are the first from controlled pre-clinical experiments that indicate that primaquine pharmacological properties can be modulated upon co-incubation/administration with drugs that are known to interact with CYP 2D6. These results highlight the potential for CYP 2D6-mediated drug-drug interactions with primaquine and indicate that the SSRI/SNRI antidepressants could be used as probe molecules to address the primaquine-CYP 2D6 DDI link in clinical studies. Additionally, CYP 2D6-mediated drug-drug interactions can be considered when examining the possible causes of human primaquine therapy failures.

X Demographics

X Demographics

The data shown below were collected from the profiles of 4 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 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Tanzania, United Republic of 1 3%
Belgium 1 3%
Unknown 31 94%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 18%
Student > Master 5 15%
Student > Ph. D. Student 3 9%
Lecturer 2 6%
Professor > Associate Professor 2 6%
Other 6 18%
Unknown 9 27%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 9 27%
Medicine and Dentistry 9 27%
Agricultural and Biological Sciences 2 6%
Biochemistry, Genetics and Molecular Biology 1 3%
Business, Management and Accounting 1 3%
Other 2 6%
Unknown 9 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 August 2023.
All research outputs
#2,954,815
of 24,276,163 outputs
Outputs from Malaria Journal
#668
of 5,802 outputs
Outputs of similar age
#49,508
of 332,337 outputs
Outputs of similar age from Malaria Journal
#14
of 150 outputs
Altmetric has tracked 24,276,163 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,802 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has done well, scoring higher than 88% 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 332,337 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 150 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.