The impact of individual human cytochrome P450 enzymes on oxidative metabolism of anticancer drug lenvatinib
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F22%3A43920651" target="_blank" >RIV/62156489:43210/22:43920651 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/22:10444763 RIV/00216305:26620/22:PU147228
Result on the web
<a href="https://doi.org/10.1016/j.biopha.2021.112391" target="_blank" >https://doi.org/10.1016/j.biopha.2021.112391</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2021.112391" target="_blank" >10.1016/j.biopha.2021.112391</a>
Alternative languages
Result language
angličtina
Original language name
The impact of individual human cytochrome P450 enzymes on oxidative metabolism of anticancer drug lenvatinib
Original language description
Lenvatinib, a small molecule tyrosine kinase inhibitor (TKI), exhibits good inhibitory effect in several types of carcinomas. Specifically, it is the most effective TKI used for treatment of thyroid cancer. To extend pharmacokinetics data on this anticancer agent, we aimed to identify the metabolites of lenvatinib formed during in vitro incubation of lenvatinib with human hepatic microsomes or recombinant cytochromes P450 (CYPs) by using high performance liquid chromatography and mass spectrometry. The role of CYPs in the oxidation of lenvatinib was initially investigated in hepatic microsomes using specific CYP inhibitors. CYP-catalytic activities in each microsomal sample were correlated with the amounts of lenvatinib metabolites formed by these samples. Further, human recombinant CYPs were employed in the metabolic studies. Based on our data, lenvatinib is metabolized to O-desmethyl lenvatinib, N-descyclopropyl lenvatinib and lenvatinib N-oxide. In the presence of cytochrome b5, recombinant CYP3A4 was the most efficient to form these metabolites. In addition, CYP1A1 significantly contributes to the lenvatinib metabolism. It was even more efficient in forming of O-desmethyl lenvatinib than CYP3A4 in the absence of cytochrome b5. The present study indicates that further research focused on drug-drug interactions, in particular on CYP3A4 and CYP1A1 modulators, is needed. This will pave new avenues towards TKIs-mediated personalized therapy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/GA18-10251S" target="_blank" >GA18-10251S: Comprehensive insight into mechanisms of action and metabolism of tyrosine kinase inhibitors and a study of ways increasing their antitumor efficiency</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicine & Pharmacotherapy
ISSN
0753-3322
e-ISSN
0753-3322
Volume of the periodical
145
Issue of the periodical within the volume
January
Country of publishing house
FR - FRANCE
Number of pages
10
Pages from-to
112391
UT code for WoS article
000724916000001
EID of the result in the Scopus database
2-s2.0-85120059147