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In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia

Overview of attention for article published in Therapeutic Drug Monitoring, April 2016
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Title
In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia
Published in
Therapeutic Drug Monitoring, April 2016
DOI 10.1097/ftd.0000000000000268
Pubmed ID
Authors

Karin Skoglund, Johan Richter, Ulla Olsson-Strömberg, Jonas Bergquist, Warunika Aluthgedara, S. J. Kumari A. Ubhayasekera, Svante Vikingsson, Anna Svedberg, Stina Söderlund, Anna Sandstedt, Anders Johnsson, Jesper Aagesen, Jonas Alsenhed, Staffan Hägg, Curt Peterson, Kourosh Lotfi, Henrik Gréen

Abstract

CYP3A metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in chronic myeloid leukemia (CML) patients. The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in CML patients. Forty-three CML patients were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to non-optimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P=0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

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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 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 19%
Other 2 13%
Professor 2 13%
Unspecified 1 6%
Student > Bachelor 1 6%
Other 2 13%
Unknown 5 31%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 31%
Medicine and Dentistry 4 25%
Unspecified 1 6%
Chemistry 1 6%
Immunology and Microbiology 1 6%
Other 0 0%
Unknown 4 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 25 July 2016.
All research outputs
#14,913,296
of 25,371,288 outputs
Outputs from Therapeutic Drug Monitoring
#801
of 1,787 outputs
Outputs of similar age
#154,383
of 314,718 outputs
Outputs of similar age from Therapeutic Drug Monitoring
#14
of 23 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,787 research outputs from this source. They receive a mean Attention Score of 4.0. This one has gotten more attention than average, scoring higher than 54% 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 314,718 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 50% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.