Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Video-Audio Media
- Keywords
- Gut microbiome, bioavailability, germ-free mice, imipenem, metabolism of drugs, pharmacokinetic of nabumetone,
- MeSH
- Anaerobiosis MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Anti-Inflammatory Agents, Non-Steroidal metabolism pharmacokinetics MeSH
- Biological Availability MeSH
- Imipenem pharmacology MeSH
- Naphthaleneacetic Acids metabolism pharmacokinetics MeSH
- Mice, Inbred BALB C MeSH
- Nabumetone metabolism pharmacokinetics MeSH
- Specific Pathogen-Free Organisms MeSH
- Rats, Wistar MeSH
- Gastrointestinal Microbiome drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Video-Audio Media MeSH
- Journal Article MeSH
- Names of Substances
- 6-methoxy-2-naphthylacetic acid MeSH Browser
- Anti-Bacterial Agents MeSH
- Anti-Inflammatory Agents, Non-Steroidal MeSH
- Imipenem MeSH
- Naphthaleneacetic Acids MeSH
- Nabumetone 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.
References provided by Crossref.org
Butyrate Treatment of DSS-Induced Ulcerative Colitis Affects the Hepatic Drug Metabolism in Mice
Gut Microbiome Alters the Activity of Liver Cytochromes P450 in Mice With Sex-Dependent Differences
