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Metabolism of primaquine in normal human volunteers: investigation of phase I and phase II metabolites from plasma and urine using ultra-high performance liquid chromatography-quadrupole time-of-flight…

Overview of attention for article published in Malaria Journal, August 2018
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3 tweeters

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4 Dimensions

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Title
Metabolism of primaquine in normal human volunteers: investigation of phase I and phase II metabolites from plasma and urine using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry
Published in
Malaria Journal, August 2018
DOI 10.1186/s12936-018-2433-z
Pubmed ID
Authors

Bharathi Avula, Babu L. Tekwani, Narayan D. Chaurasiya, Pius Fasinu, N. P. Dhammika Nanayakkara, H. M. T. Bhandara Herath, Yan-Hong Wang, Ji-Yeong Bae, Shabana I. Khan, Mahmoud A. Elsohly, James D. McChesney, Peter A. Zimmerman, Ikhlas A. Khan, Larry A. Walker

Abstract

Primaquine (PQ), an 8-aminoquinoline, is the only drug approved by the United States Food and Drug Administration for radical cure and prevention of relapse in Plasmodium vivax infections. Knowledge of the metabolism of PQ is critical for understanding the therapeutic efficacy and hemolytic toxicity of this drug. Recent in vitro studies with primary human hepatocytes have been useful for developing the ultra high-performance liquid chromatography coupled with high-resolution mass spectrometric (UHPLC-QToF-MS) methods for simultaneous determination of PQ and its metabolites generated through phase I and phase II pathways for drug metabolism. These methods were further optimized and applied for phenotyping PQ metabolites from plasma and urine from healthy human volunteers treated with single 45 mg dose of PQ. Identity of the metabolites was predicted by MetaboLynx using LC-MS/MS fragmentation patterns. Selected metabolites were confirmed with appropriate standards. Besides PQ and carboxy PQ (cPQ), the major plasma metabolite, thirty-four additional metabolites were identified in human plasma and urine. Based on these metabolites, PQ is viewed as metabolized in humans via three pathways. Pathway 1 involves direct glucuronide/glucose/carbamate/acetate conjugation of PQ. Pathway 2 involves hydroxylation (likely cytochrome P450-mediated) at different positions on the quinoline ring, with mono-, di-, or even tri-hydroxylations possible, and subsequent glucuronide conjugation of the hydroxylated metabolites. Pathway 3 involves the monoamine oxidase catalyzed oxidative deamination of PQ resulting in formation of PQ-aldehyde, PQ alcohol and cPQ, which are further metabolized through additional phase I hydroxylations and/or phase II glucuronide conjugations. This approach and these findings augment our understanding and provide comprehensive view of pathways for PQ metabolism in humans. These will advance the clinical studies of PQ metabolism in different populations for different therapeutic regimens and an understanding of the role these play in PQ efficacy and safety outcomes, and their possible relation to metabolizing enzyme polymorphisms.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 13%
Student > Master 2 13%
Other 2 13%
Professor 1 7%
Student > Doctoral Student 1 7%
Other 5 33%
Unknown 2 13%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 3 20%
Medicine and Dentistry 3 20%
Biochemistry, Genetics and Molecular Biology 2 13%
Chemistry 2 13%
Physics and Astronomy 1 7%
Other 2 13%
Unknown 2 13%

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 14 August 2018.
All research outputs
#8,378,093
of 13,370,991 outputs
Outputs from Malaria Journal
#2,942
of 3,900 outputs
Outputs of similar age
#159,523
of 266,755 outputs
Outputs of similar age from Malaria Journal
#1
of 1 outputs
Altmetric has tracked 13,370,991 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,900 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. 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 266,755 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them