Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Clinical experience of the tolerance of mesalazine and olsalazine in patients intolerant of sulphasalazine. Effects of mesalazine substitution on salicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis. Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis. Studies of two novel sulfasalazine analogs, ipsalazide and balsalazide Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis. AN EXPERIMENT TO DETERMINE THE ACTIVE THERAPEUTIC MOIETY OF SULPHASALAZINE Double‐blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis
To compare the disposition of  5-aminosalicylic acid ( 5-ASA ) and its acetylated metabolite during treatment with olsalazine and mesalazine , 14 patients with inactive ulcerative colitis were r and omly assigned to olsalazine ( 1 g twice daily ) and the mesalazines , Asacol ( 800 + 400 + 800 mg daily ) , Pentasa ( 750 + 500 + 750 mg daily ) , and Salofalk ( 750 + 500 + 750 mg daily ) in a crossover design trial so that all received each drug for seven days . Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces . A predose serum sample and a 24 hour urine collection were obtained on day seven . The 5-ASA and acetyl-5-aminosalicylic acid ( Ac-5-ASA ) values were determined by high performance liquid chromatography . Olsalazine almost doubled the colonic concentrations ( mean 23.7 ( SEM ) ( 1.9 ) mmol/l ) of its therapeutically active ingredient ( 5-ASA ) compared with equimolar doses of Pentasa ( 12.6 ( 2.2 ) mmol/l ; p less than 0.0003 ) and Salofalk ( 15.0 ( 2.0 ) mmol/l ; p less than 0.003 ) . At the same time , olsalazine treatment was associated with lower serum concentrations and urinary excretions ( p less than 0.05 ) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations . The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment We assessed the tolerance and safety of two new preparations design ed to release 5-aminosalicylic acid in the colon in patients with ulcerative colitis who were intolerant of sulphasalazine .  Twenty-eight of 37 patients ( 76 % ) given mesalazine and 18 of 21 patients ( 86 % ) given olsalazine  tolerated the new preparations with no adverse effects . No haematologic or biochemical abnormalities were detected . Adverse reactions to the new preparations were usually but not always similar to those they had previously encountered with sulphasalazine , but a few patients experienced rash and diarrhoea . In some patients intolerant of one of the new preparations , their tolerance of the other was assessed . Three patients intolerant of mesalazine  tolerated olsalazine .  Similarly , three other patients intolerant of olsalazine  tolerated mesalazine .  We conclude that not all adverse effects of sulphasalazine are due to the sulphapyridine part of the molecule . Some are due to the released 5-aminosalicylic acid and some to the parent compound . Both drugs are likely to prove useful in the management of patients intolerant of sulphasalazine Some semen characteristics of eight male patients with clinical ly inactive ulcerative colitis were investigated . Semen analysis was carried out twice during salicylazosulfapyridine ( SASP ) treatment and repeated twice after at least 3 months ' treatment with mesalazine . The motility variables all showed significant improvement during mesalazine treatment : the grade d motility ( p less than 0.05 ) , motility in percentage ( p less than 0.01 ) , and the penetration in egg white ( p less than 0.05 ) . The semen plasma was analyzed for mesalazine and the metabolite Ac-mesalazine during both regimens . There was no difference in the semen plasma concentration of mesalazine during the two regimens , whereas Ac-mesalazine was significantly higher during mesalazine treatment than during SASP treatment , indicating that other SASP metabolites , most likely sulfapyridine , are the agent causing the abnormal sperm characteristics . We suggest that pure mesalazine preparations are a safer alternative in young men with chronic inflammatory bowel disease PURPOSE We conducted a prospect i ve study to determine the effects of nonadherence with mesalamine among patients with quiescent ulcerative colitis . METHODS We followed a cohort of 99 consecutive patients who had ulcerative colitis in remission for more than 6 months and who were taking maintenance mesalamine .  Medication adherence rates were calculated based on pharmacy records and a vali date d formula . Nonadherence was defined as refilling less than 80 % of prescribed medication . Patients were followed prospect ively and evaluated either in clinic or via telephone at 6 , 12 , and 24 months . The primary outcome was clinical recurrence of ulcerative colitis . Proportional hazards models were used to adjust for confounders . RESULTS At 6 months , 12 patients ( 12 % ) had clinical recurrence of disease symptoms , all of whom were nonadherent with medication . At 12 months , 19 of 86 patients had recurrent disease , 13 ( 68 % ) of whom were nonadherent . Patients who were not adherent with medication had more than a fivefold greater risk of recurrence than adherent patients ( hazard ratio = 5.5 ; 95 % confidence interval : 2.3 to 13 ; P < 0.001 ) . CONCLUSION Nonadherence with medication increases the risk of clinical relapse among patients with quiescent ulcerative colitis . Future research should be directed at behavioral interventions to improve adherence Sulfasalazine appears to exert its beneficial effect in colitis by releasing 5-aminosalicylic acid in the colon , but its use can be limited by side effects . Ipsalazide and balsalazide are novel sulfasalazine analogs design ed to release 5-aminosalicylic acid and a nontoxic carrier molecule in the gastrointestinal tract . They have a low oral toxicity following single or repeat administration to mouse , rat , and ferret , and balsalazide is not mutagenic in the Ames test . Ipsalazide and balsalazide are split in rat and man , and the urinary and fecal excretion pattern of the 5-aminosalicylic acid released is similar to that of sulfasalazine ; the carrier molecules are absorbed to a lesser extent than the sulfapyridine derived from sulfasalazine . These two analogs deserve therapeutic trial To determine the influence of inflammation and topical treatment with 5-aminosalicylic acid or prednisolone on arachidonic acid metabolism in vivo , we carried out a double-blind controlled study on the release of prostagl and in E2 and leukotriene B4 to the rectal lumen in 24 consecutive patients with proven distally located ulcerative colitis . Before and at days 15 and 29 a dialysis bag was placed in the emptied rectum for 4 h prior to assessing clinical , endoscopic , and histologic disease activity . A single enema was given daily at bedtime ( 1 g 5-aminosalicylic acid or 25 mg prednisolone ) until complete remission or for a maximum of 4 wk . Clinical and endoscopic remission was obtained in 16 ( 7 on 5-aminosalicylic acid ) and 11 ( 3 on 5-aminosalicylic acid ) patients , respectively . Luminal concentrations of prostagl and in E2 and leukotriene B4 were positively correlated to disease activity and significantly decreased among the prednisolone-treated patients . In both treatment groups a decrease toward normal levels occurred in patients responding to therapy . In retrospect , the pretreatment prostagl and in E2 and leukotriene B4 levels were significantly higher in patients not responding to therapy than in those improving during treatment . In conclusion , luminal prostagl and in E2 and leukotriene B4 levels may prove more useful predictors of the outcome of treatment in relapsing ulcerative colitis than clinical indices of disease activity Sulphasalazine ( S.A.S.P. ) is of proven value in the treatment of ulcerative colitis , but its mode of action is unknown . When it is taken by mouth , nearly all the dose reaches the colon intact , where it is split by bacteria into sulphapyridine ( S.P. ) and 5-aminosalicylic acid ( 5-A.S.A. ) . An experiment was devised to determine whether the therapeutic property of S.A.S.P. is a function of the parent molecule or of these two principal metabolites . Retention enemas of S.A.S.P. , S.P. , and 5-A.S.A. were administered to volunteer patients with sigmoidoscopic evidence of active ulcerative colitis . The experiment was conducted as a blind controlled therapeutic trial , each patient having one of the test enemas daily for two weeks . Pronounced histological improvement was observed in approximately 30 % of the patients receiving S.A.S.P. or 5-A.S.A. , and in only 5 % of those receiving S.P. It is concluded that the active therapeutic moiety of S.A.S.P. IS 5-A.S.A. and that the S.P. functions as a carrier ensuring that the 5-A.S.A. is liberated within the colon Aminosalicylates are used as st and ard treatment for maintaining remission in ulcerative colitis . As yet , there is no other existing alternative with proven efficacy . In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis , a trial was conducted to test the effects of probiotic treatment with an oral preparation of non‐pathogenic E. coli
BACKGROUND Oral 5-aminosalicylic ( 5-ASA ) preparations were intended to avoid the adverse effects of sulfasalazine ( SASP ) while maintaining its therapeutic benefits .
Previously , it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP .
This up date d review includes more recent studies and evaluates the effectiveness , dose-responsiveness , and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis .
OBJECTIVES The primary objectives were to assess the efficacy , dose-responsiveness and safety of oral 5-ASA compared to placebo , SASP , or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis .
A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional ( two or three times daily ) dosing regimens .