An Ex Vivo Fermentation Screening Platform to Study Drug Metabolism by Human Gut Microbiota

Drug Metabolism and Disposition : the Biological Fate of Chemicals
E van de SteegW H J Vaes

Abstract

Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug pharmacokinetics, efficacy, and safety is largely unknown. To investigate human colon microbiota-mediated drug metabolism, we applied a recently developed ex vivo fermentation screening platform, in which human colonic microbiota conditions are simulated. A set of 12 drugs (omeprazole, simvastatin, metronidazole, risperidone, sulfinpyrazone, sulindac, levodopa, dapsone, nizatidine, sulfasalazine, zonisamide, and acetaminophen) was incubated with human colon microbiota under strictly anaerobic conditions, and samples were analyzed using high-performance liquid chromatograph-UV-high-resolution mass spectrometry analysis. The human microbiota in the fermentation assay consisted of bacterial genera regularly encountered in human colon and fecal samples and could be reproducibly cultured in independent experiments over time. In addition, fully anaerobic culture conditions could be maintained for 24 ...Continue Reading

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Citations

Oct 20, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Aarti Sawant-Basak, R Scott Obach
May 7, 2020·Frontiers in Endocrinology·Samantha Alvarez-HerreraLenin Pavón
Apr 11, 2020·Translational and Clinical Pharmacology·Sihyun ChaeJoo-Youn Cho
Jun 20, 2020·Drug Metabolism Reviews·Lianne J StevensEvita van de Steeg
Mar 19, 2021·Molecular Systems Biology·Michael ZimmermannLisa Maier
Aug 14, 2020·Cell Host & Microbe·P FangE Y Hsiao
Aug 14, 2021·Acta Pharmaceutica Sinica. B·Xintong ZhangZhonggao Gao
Sep 2, 2021·Drug Discovery Today·Lap Hing ChiRobin L Anderson
Dec 24, 2021·Pharmacology Research & Perspectives·Ana I LoureiroPatricio Soares-da-Silva

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