A mechanism-based understanding of altered drug pharmacokinetics by gut microbiota

Mechanisms and Clinical Implications of Human Gut Microbiota-Drug Interactions in the Precision Medicine Era

“…For instance, sulfasalazine, a prodrug used in the treatment of inflammatory bowel disease (IBD), undergoes reduction by the gut microbiota, liberating 5-aminosalicylic acid (5-ASA), the biologically active antiinflammatory component [22]. Similarly, balsalazide and olsalazine are prodrugs relying on gut microbiota-mediated reduction to release 5-ASA [23]. Metronidazole, an antibiotic featuring a nitro group, also needs gut microbiota to be reduced to its toxic radical [24].…”

“…This metabolic process can have significant implications for drug development, as it can influence the bioavailability, efficacy, toxicity, and inter-individual variability of the prodrugs. The metabolic process can be direct or indirect, depending on whether the prodrug is transformed by the gut bacteria or by the host enzymes affected by the gut bacteria [23]. Therefore, to optimize the design and delivery of prodrugs, and to improve their therapeutic outcomes, it is important to understand how various factors affect the gut microbial metabolism of prodrugs [119,120].…”

“…The establishment of meticulously standardized protocols for investigating interactions between the gut microbiota and drugs assumes paramount importance in ensuring consistent research outcomes. This necessitates the standardization of methodologies encompassing sample collection, storage, and processing, as well as the rigorous application of uniform procedures for data analysis and interpretation [23]. A second pivotal issue lies in the ethical dimension.…”