Tissue and Bacterial Splitting of Sulphasalazine

Abstract

1. The cleavage of sulphasalazine at the azo bond by bacterial suspensions and tissue homogenates has been studied in vitro. 2. For maximum activity the azo reductase system requires anaerobic conditions and the presence of cofactors, namely NADPH and FAD. in this respect, sulphasalazine resembles other azo dyes. 3. Under optimum conditions all the species of bacteria tested were capable of splitting sulphasalazine and there were no major differences in the degree of activity shown by different species. The enzyme system is located within the bacterial cell and does not leak out of it. 4. All the tissues tested, both human and rat, showed azo reductase activity. The liver showed a much higher activity than the other tissues.

Sulfasalazine in ionic liquid form with improved solubility and exposure

“…It is known that sulfasalazine is metabolized via reduction (by reductases) to form sulfapyridine and 5-amino salicylic acid. 35 Some reports suggest that this metabolism is mediated by gut microflora, 36 while others suggest the involvement of gut and hepatic reductase enzymes. 37 Because the two major metabolites were detected in the rat S9 incubations, the metabolic stability assessments for sulfasalazine and its IL form were carried out in rat liver S9 fractions.…”

Pharmacomicrobiomics: Influence of gut microbiota on drug and xenobiotic metabolism

“…Sulfasalazine is a combination of aminosalicylate and sulfapyridine by an azo bond, as sulfasalazine is not absorbed rapidly by the upper gastrointestinal tract, but its azo bond in the colon is decomposed by gut bacteria into sulfapyridine, which is absorbed and mesalazine (5‐aminosalicylic acid), which is activated in the colon 23 . In a pharmacokinetic study using healthy volunteers, it was found that intestinal microbiota are essential for the activation of sulfasalazine which helps us understand why the drug is more effective in ulcerative colitis than in Chron's disease 47 . The rate of metabolism of sulfasalazine by the gut microbiota can be improved by administration of probiotics strains such as Lactobacillus acidophilus L10, Bifidobacterium lactis B94, and Streptococcus salivarius K12 alongside.…”

“…23 In a pharmacokinetic study using healthy volunteers, it was found that intestinal microbiota are essential for the activation of sulfasalazine which helps us understand why the drug is more effective in ulcerative colitis than in Chron's disease. 47 The rate of metabolism of sulfasalazine by the gut microbiota can be improved by administration of probiotics strains such as Lactobacillus acidophilus L10, Bifidobacterium lactis B94, and Streptococcus salivarius K12 alongside. In an in vitro study, it was observed that after incubation of the contents of rat colon with sulfasalazine plus probiotics or sulfasalazine alone under anaerobic conditions, the probiotics possessed azoreductase activity and a corresponding ability to metabolize sulfasalazine.…”

Disease‐modifying Antirheumatic Drugs in Rheumatoid Arthritis: Current Concepts

“…The drug is poorly absorbed from the small intestine and is split in the colon into sulphapyridine and 5-aminosalicylic acid. 12 In patients with RA, the combination molecule has been shown to be more effective than the individual components (unlike inflammatory bowel disease, in which aminosalicylic acid alone is effective). 13 Sulphasalazine is started at an initial dose of 500 mg, increasing up to 2 or 3 g/day.…”