Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F19%3A00518679" target="_blank" >RIV/61388971:_____/19:00518679 - isvavai.cz</a>
Alternative codes found
RIV/68378041:_____/19:00518444 RIV/61989592:15110/19:73594113 RIV/00216208:11160/19:10410232
Result on the web
<a href="https://www.tandfonline.com/doi/full/10.1080/00498254.2018.1558310?scroll=top&needAccess=true" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/00498254.2018.1558310?scroll=top&needAccess=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/00498254.2018.1558310" target="_blank" >10.1080/00498254.2018.1558310</a>
Alternative languages
Result language
angličtina
Original language name
Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome
Original language description
1. The underlying microbial metabolic activity toward xenobiotics is among the least explored factors contributing to the inter-individual variability in drug response. 2. Here, we analyzed the effect of microbiota on a non-steroidal anti-inflammatory drug nabumetone. 3. First, we cultivated the drug with the selected gut commensal and probiotic bacteria under both aerobic and anaerobic conditions and analyzed its metabolites by high-performance liquid chromatography (HPLC) with UV detection. To analyze the effect of microbiota on nabumetone pharmacokinetics in vivo, we administered a single oral dose of nabumetone to rodents with intentionally altered gut microbiome - either rats treated for three days with the antibiotic imipenem or to germ-free mice. Plasma levels of its main active metabolite 6 methoxy-2-naphthylacetic acid (6-MNA) were analyzed at pre-specified time intervals using HPLC with UV/fluorescence detection. 4. We found that nabumetone is metabolized by bacteria to its non-active metabolites and that this effect is stronger under anaerobic conditions. Although in vivo, none of the pharmacokinetic parameters of 6-MNA was significantly altered, there was a clear trend towards an increase of the AUC, Cmax and t(1/2) in rats with reduced microbiota and germ-free mice.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/GA17-09869S" target="_blank" >GA17-09869S: Gut microbiota in pharmacotherapy of digestive diseases</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Xenobiotica
ISSN
0049-8254
e-ISSN
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Volume of the periodical
49
Issue of the periodical within the volume
11
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
1296-1302
UT code for WoS article
000481895400006
EID of the result in the Scopus database
2-s2.0-85062331907