On the Colonic Bacterial Metabolism of Azo-Bonded Prodrugsof 5-Aminosalicylic Acid

In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model

“…Many drugs are substrates for colonic bacteria, which could result in degradation and influence their bioavailability. 9,10 These arguments also support that the permeability and the absorptive capacity for drugs of the colonic membrane are considered lower than the small intestine. However, this is not always so simple.…”

“…In addition, the gastrointestinal tract is populated with a large number of bacteria and most of them reside in the large intestine; the stability of a drug to the microbiota is clinically relevant; the metabolism can transform a drug in pharmacologically active, inactive, or toxic. Many drugs are substrates for colonic bacteria, which could result in degradation and influence their bioavailability . These arguments also support that the permeability and the absorptive capacity for drugs of the colonic membrane are considered lower than the small intestine.…”

The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism

“…Azoreductases are widespread across multiple bacterial phyla found in the human gut 28 and possess broad substrate compatibility 43, 44 ; however, they metabolize azo compounds at different rates depending on the broader chemical structure of the molecule 45 . Gut microorganisms can also metabolize the downstream metabolites of azo reductions.…”

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…As these bacteria are most abundant in the colon, the therapeutic activity of the drug is mainly triggered at this level. 25 The involvement of gut microbiota in modulating doxorubicin toxicity at the intestinal level has long been known and was mainly ascribed to an increase of epithelial permeability, as described above. However, the different effects exerted by gut bacteria at different levels of the intestinal tracts remained unexplained: apparently protective for the colonic epithelium, damaging for the small intestine.…”

“…Azoreductases produced by many enteric species, mostly belonging to genera Clostridium and Eubacterium (Firmicutes), play a fundamental role in the activation of the azo‐bonded prodrugs of 5‐aminosalicylic acid used to treat patients with ulcerative colitis and Crohn's disease, as they cleave the azoic bond, releasing the active moiety 5‐aminosalicylic acid. As these bacteria are most abundant in the colon, the therapeutic activity of the drug is mainly triggered at this level …”