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Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers

Overview of attention for article published in Clinical Pharmacology & Therapeutics, March 2003
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  • Above-average Attention Score compared to outputs of the same age and source (56th percentile)

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Title
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers
Published in
Clinical Pharmacology & Therapeutics, March 2003
DOI 10.1067/mcp.2003.28
Pubmed ID
Authors

Michael H. Skinner, Han‐Yi Kuan, Alan Pan, Korbtham Sathirakul, Mary Pat Knadler, Celedon R. Gonzales, Kwee Poo Yeo, Shobha Reddy, Maggie Lim, Mosun Ayan‐Oshodi, Stephen D. Wise

Abstract

Duloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2). Subjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady-state duloxetine 60 mg twice daily. In study 2, steady-state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady-state paroxetine 20 mg once daily. Duloxetine increased the maximum plasma concentration of desipramine 1.7-fold and the area under the concentration-time curve 2.9-fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration-time curve at steady state 1.6-fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine. Duloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Other 9 20%
Researcher 7 16%
Student > Ph. D. Student 4 9%
Student > Master 4 9%
Student > Bachelor 3 7%
Other 9 20%
Unknown 9 20%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 9 20%
Medicine and Dentistry 9 20%
Biochemistry, Genetics and Molecular Biology 3 7%
Business, Management and Accounting 3 7%
Agricultural and Biological Sciences 3 7%
Other 5 11%
Unknown 13 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 02 April 2013.
All research outputs
#6,381,735
of 24,827,122 outputs
Outputs from Clinical Pharmacology & Therapeutics
#1,387
of 4,424 outputs
Outputs of similar age
#16,940
of 57,984 outputs
Outputs of similar age from Clinical Pharmacology & Therapeutics
#7
of 16 outputs
Altmetric has tracked 24,827,122 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 4,424 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.9. This one has gotten more attention than average, scoring higher than 68% 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 57,984 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 70% of its contemporaries.
We're also able to compare this research output to 16 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 56% of its contemporaries.