Evidence map›Paper›PMID 27188854›Full record

ArticleMalaria journal2016

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

Xiannu Jin, Brittney Potter, Thu-Lan Luong, Jennifer Nelson, Chau Vuong, Corttney Potter, Lisa Xie, Jing Zhang, Ping Zhang, Jason Sousa and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Malaria journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.0field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Antimicrobial agents and chemotherapy · 2019
    Trial
  2. Article
  3. Review
  4. Retrospective Evaluation of Drug-Drug Interactions With Erlotinib and Gefitinib Use in the Military Health System.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 8-Aminoquinoline Therapy for Latent Malaria.Clinical microbiology reviews · 2019
    Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Xiannu JinMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Brittney PotterMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Thu-Lan LuongMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Jennifer NelsonMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Chau VuongMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Corttney PotterMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Lisa XieMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Jing ZhangMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Ping ZhangMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Jason SousaMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Qigui LiMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Brandon S PybusMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Mara Kreishman-DeitrickMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Mark HickmanMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Philip L SmithMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Robert ParisMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Gregory ReichardMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA.
Sean R MarcsisinMilitary Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD, 20910, USA. sean.r.marcsisin.mil@mail.mil.
Walter Reed Army Institute of Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

methodsIn 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.

resultsThe 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.

conclusionsThese 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.

Indexed as

Drug InteractionsAnimalsAntidepressive AgentsAntimalarialsCells, CulturedCytochrome P-450 CYP2D6Disease Models, AnimalFemaleHepatocytesHumansInhibitory Concentration 50MalariaMaleMiceMice, Inbred C57BLPrimaquineAntidepressive AgentsAntimalarialsCytochrome P-450 CYP2D6PrimaquineSerotonin and Noradrenaline Reuptake InhibitorsAntimalarialCYP 2D6Drug–drug interactionsDrug metabolismPharmacokineticsPrimaquineRelapsing malaria

Identifiers

PMID27188854
PMCPMC4869338
OpenAlexW2403162773

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.