Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, audiovizuální média
- Klíčová slova
- Gut microbiome, bioavailability, germ-free mice, imipenem, metabolism of drugs, pharmacokinetic of nabumetone,
- MeSH
- anaerobióza MeSH
- antibakteriální látky farmakologie MeSH
- antiflogistika nesteroidní metabolismus farmakokinetika MeSH
- biologická dostupnost MeSH
- imipenem farmakologie MeSH
- kyseliny naftalenoctové metabolismus farmakokinetika MeSH
- myši inbrední BALB C MeSH
- nabumeton metabolismus farmakokinetika MeSH
- organismy bez specifických patogenů MeSH
- potkani Wistar MeSH
- střevní mikroflóra účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- Názvy látek
- 6-methoxy-2-naphthylacetic acid MeSH Prohlížeč
- antibakteriální látky MeSH
- antiflogistika nesteroidní MeSH
- imipenem MeSH
- kyseliny naftalenoctové MeSH
- nabumeton MeSH
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 t1/2 in rats with reduced microbiota and germ-free mice.
Citace poskytuje Crossref.org
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