Influence of intestinal transit time on azo-reduction of salicylazosulphapyridine (Salazopyrin).

Abstract

SUMMARY During a normal and an accelerated intestinal transit, in seven healthy volunteers, the recoveries of salicylazosulphapyridine (SASP) and its split products sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) were determined in urine and faeces. The azo-reduction of SASP and consequently the recovery of 5-ASA in the faeces was found to be substantially decreased during an accelerated intestinal transit. In addition, in 18 patients with inflammatory disease of the colon during maintenance therapy of SASP it could be demonstrated that the serum SP levels were related to the diarrhoeal state and did not correlate with disease activity. As recent studies have reported that 5-ASA is possibly the active therapeutic moiety of SASP, the ineffectiveness of SASP therapy in patients with active colitis may be ascribed to the reduced azo reduction of SASP as the result of profuse diarrhoea.Salicylazosulphapyridine (Salazopyrin, Sulphasalazine, SASP) has been widely used in the treatment of ulcerative colitis and Crohn's disease. However, its mode of action is still unknown. SASP is composed of sulphapyridine (SP) in azo-linkage with 5-aminosalicylic acid (5-ASA). After an oral dose of SASP in man, only a small fraction has been found to be absorbed in the small bowel and excreted in the urine. The greater part of the drug reaches the colon and is almost completely split at the diazo bond by bacterial azo-reductases into SP and 5-ASA (Schroder and Campbell, 1972;Peppercorn and Goldman, 1973). SP is then mostly absorbed and subsequently partially metabolised in the liver (acetylation and glucuronidation) before excretion in the urine. The 5-ASA moiety is largely recovered in the faeces and only a small portion is found in the urine as acetylated form.As SASP is particularly effective in the treatment of inflammatory disease of the large bowel, it has been suggested that one of the metabolites, rather than SASP itself, is responsible for the drug's activity at the site of breakdown. Although controlled trials have established the value of SASP in

Effects of Ischaemic Heart Disease, Crohnʼs Disease and Antimicrobial Therapy on the Pharmacokinetics of Sulphinpyrazone

“…Sulphasalazine, which is used to treat this condition and is metabolised to 5'-aminosalicylate and sulphapyridine primarily by the bacteria within the large bowel (Schroder et al 1973) undergoes less extensive metabolism when relapse occurs (Azad Khan & Truelove 1980). Similarly, the administration of the laxative, bisacodyl, substantially reduces the metabolism of sulphasalazine (Van Hees et al 1979). Thus, disease states or the coadministration of drugs which increase the motility of the intestine might also affect the formation of sulphinpyrazone sulphide.…”

Balsalazide disodium for the treatment of ulcerative colitis

“…Given that balsalazide relies on colonic bacteria for its activity, it has been speculated whether concomitant antibiotic treatment or an individual's colonic flora can affect its efficacy. Although there are reports of decreased azo-reduction in the setting of profuse diarrhea [17], and a third reduction in the cleavage of sulfasalazine after a course of ampicillin antibiotics [18], this does not appear to be a common clinical issue.…”

Delayed‐release mesalazine (5‐aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

“…However, following colonic delivery these prodrugs must also undergo bacterial azoreduction before releasing 5-ASA. Although this process is usually highly efficient it may be considerably impaired by both rapid transit (van Hees et al, 1979) and antibiotic exposure (Houston et al, 1982), and is therefore a further potential source of reduced bioavailability.…”