Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome

0518679 - MBÚ 2020 RIV GB eng J - Článek v odborném periodiku
Jourová, L. - Anzenbacher, P. - Matušková, Z. - Večeřa, R. - Strojil, J. - Kolář, M. - Nobilis, M. - Hermanová, Petra - Hudcovic, Tomáš - Kozáková, Hana - Kverka, Miloslav - Anzenbacherová, E.
Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome.
Xenobiotica. Roč. 49, č. 11 (2019), s. 1296-1302. ISSN 0049-8254. E-ISSN 1366-5928
Grant CEP: GA ČR(CZ) GA17-09869S
Institucionální podpora: RVO:61388971
Klíčová slova: Gut microbiome * pharmacokinetic of nabumetone * germ-free mice
Obor OECD: Pharmacology and pharmacy
Impakt faktor: 1.902, rok: 2019
Způsob publikování: Omezený přístup
https://www.tandfonline.com/doi/full/10.1080/00498254.2018.1558310?scroll=top&needAccess=true

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.
Trvalý link: http://hdl.handle.net/11104/0303753