Pharmacological and biochemical actions of sulphasalazine.

This review considers recent pharmacological and biochemical studies of sulphasalazine and its colonic metabolites, 5-aminosalicylic acid and sulphapyridine, in relation to the use of the parent drug for the treatment of ulcerative colitis and, more recently, rheumatoid arthritis. Several factors make it difficult to analyse the mode of action of sulphasalazine, such as the aetiology and variable course of the conditions it is used to treat, lack of suitable animal models, and the question of which moiety of the drug is active. An important feature of the pharmacokinetics of the drug after oral administration is the significance of the azo cleavage of sulphasalazine due to bacterial action. The effects of sulphasalazine on the metabolism of arachidonic acid to prostaglandins and leukotrienes have been widely studied because of the evidence that these substances are formed in increased amounts in inflammatory bowel diseases. The effects are complex, but it appears that sulphasalazine and 5-aminosalicylic acid are weak and very weak inhibitors, respectively, of both cyclo-oxygenase- and lipoxygenase-dependent pathways. The overall pharmacological profile may favour a more marked inhibition of the lipoxygenase pathway because of the additional ability of 5-aminosalicylic acid to enhance prostanoid production and of sulphasalazine to inhibit prostaglandin inactivation. Drugs with selective lipoxygenase inhibitory actions in the colon should thus be sought so as not to compromise the prostaglandin pathway. Other properties of sulphasalazine, including its immunosuppressive, antifolate, lymphocyte inhibitory and leucocyte modulatory actions, are also discussed in the context of the therapeutic uses of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)