Rectal administration of d-alpha tocopherol for active ulcerative colitis： A preliminary report

AIM： To investigate the anti-oxidant and antineutrophil recruitment effects of rectal d-alpha （d-α） tocopherol administration on mild and moderately active ulcerative colitis （UC）.
METHODS： Fifteen patients with mild and moderately active ulcerative colitis were enrolled in an openlabel study of d-α tocopherol enema （8000 U/d） for 12 wk. All patients were receiving concomitant therapy with 5-aminosalicylic acid derivatives （5-ASA） and/or immunomodulator medications. Endoscopic evaluation was performed at baseline and after 4th and 12th weeks. Disease activity was measured with the Mayo disease activity index （DAI） and remission was defined as DAI of ≤ 2 with no blood in stool. Clinical response was defined as a DAI reduction of ≥ 2.
RESULTS： At the end of 12th week, the average DAI score significantly decreased compared to the beginning of the study （2.3 ± 0.37 vs 8 ± 0.48, P 〈 0.0001）. One patient was withdrawn after 3 wk for being unavailable to follow-up. On the 4th week of therapy, 12 patients showed clinical response, 3 of whom （21.4%） achieving remission. After 12 wk, all 14 patients responded clinically to the therapy and remission was induced in 9 of them （64%）. No patient reported adverse events or was hospitalized due to worsened disease activity.
CONCLUSION： This preliminary report suggests that rectal d-α tocopherol may represent a novel therapy for mild and moderately active UC. The observed results might be due to the anti-inflammatory and anti-oxidative properties of vitamin E.     

Effect of weekend 5-aminosalicylic acid (mesalazine) enema as maintenance therapy for ulcerative colitis: results from a randomized controlled study

BACKGROUND: 5-aminosalicylic acid (5-ASA) is known to be effective in the treatment of active ulcerative colitis (UC). The aim of the current study was to investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when administered twice weekly as a weekend treatment regimen, compared to daily oral 5-ASA alone. We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school. METHODS: Between January 2004 and August 2005, patients with UC, in whom remission of the condition had just been induced, were randomly assigned to either: the weekend 5-ASA enema group (n=11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group (n=13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of the study was defined as the incidence of relapse. The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5-ASA enema group. RESULTS: In the weekend enema group, 2 patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only group. The multivariate hazard ratio of relapse associated with weekend 5-ASA enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04-0.94). CONCLUSIONS: This study demonstrated the beneficial effects of adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC.     

Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used frequently in the treatment of ulcerative colitis. However, there have been few reports investigating the relationship between colonic mucosal concentrations of 5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were administered. The aim of this study is to compare the mucosal concentrations of 5-ASA ensured by sulfasalazine or mesalamine, and to define the clinical significance of the measurement of 5-ASA concentrations in the treatment of distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow-release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal administration of 5-ASA. High-pressure liquid chromatography was used to measure the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA concentrations of the sulfasalazine group with the mesalamine group. Furthermore, we analyzed the relationship between tissue 5-ASA concentrations and the Disease Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in the sulfasalazine group were higher than those in the group taking oral mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the patients who received oral and rectal mesalamine in an enema than in the patients who had oral mesalamine alone. There was a significant inverse correlation between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001). CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was significantly higher in the sulfasalazine group than in the mesalamine group. Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the estimation of its efficacy in the treatment of ulcerative colitis.     

Oral Beclomethasone Dipropionate as an Alternative to Systemic Steroids in Mild to Moderate Ulcerative Colitis Not Responding to Aminosalicylates

Backgroud  

Aminosalicylates (5-ASA) are first-line treatment for mild-moderate ulcerative colitis (UC). Systemic corticosteroids (CS) are considered for patients in whom 5-ASA has been unsuccessful, but their use is limited by adverse effects. Beclomethasone dipropionate (BDP), a topically acting steroid with low systemic bioavailability, has a more favorable safety profile, but its role in clinical practice is not yet well established.     

Efficacy and safety of mesalamine 1 g HS versus 500 mg BID suppositories in mild to moderate ulcerative proctitis: a multicenter randomized study

BACKGROUND: Ulcerative proctitis (UP) usually presents as fresh rectal bleeding. Successful treatment using topical mesalamine 5-aminosalicyclic acid (5-ASA) 500 mg BID suppository led to developing a once-a-day formulation that could contribute to better acceptability and ease of use by patients. The objective of this randomized trial, conducted in 18 centers, was to compare efficacy of 2 modes of treatment with 5-ASA suppositories. METHODS: Ninety-nine patients with mild or moderate UP limited to 15 cm of the anal margin, evidenced by a disease activity index (DAI) between 4 and 11, were randomized to 5-ASA 500 mg suppository (Canasa; Axcan Pharma) BID or 1 g at bedtime (HS) for 6 weeks. The study used a noninferiority hypothesis based on the mean difference in DAI values after 6 weeks of treatment on an intent-to-treat basis using analysis of covariance. DAI was derived from a composite of the measures of stool frequency, rectal bleeding, mucosal visualization at endoscopy, and general well being. RESULTS: There was no difference between groups at baseline for demographic and clinical parameters. Mean DAIs fell from 6.6 +/- 1.5 (SD) to 1.6 +/- 2.3 in the 500 mg BID group (n = 48) and from 6.1 +/- 1.5 to 1.3 +/- 2.2 in the 1 g HS group (n = 39). There was no significant difference (P = 0.74) in mean DAI at week 6 between the 2 groups. Both groups showed a significant reduction (P < 0.0001) in DAI over the course of the 6 weeks. Both formulations showed effectiveness in reducing each individual component of the DAI. There was no significant difference between treatments in adverse events, and both groups had an overall drug compliance of greater than 95%. CONCLUSION: This study showed that 1 g HS and 500 mg BID mesalamine suppository treatments of UP patients were equivalent in all facets of efficacy, safety, and compliance in a 6-week trial.     

布地奈得和氢化可的松灌肠治疗溃疡性结肠炎的对比研究

目的:本实验对比观察布地奈得(BUD)和氢化可的松(HD)灌肠治疗轻中度远段溃疡性结肠炎(UC)的疗效 及副反应:建立高效液相色谱仪(HPLC)检测血和结肠粘膜中HD浓度的方法 方法:随机对照单(?)观察BUD组12例 HD组19例UC患者 治疗两周,比较两组在临床症状,结肠镜下,组织学及William疾病活动指数(DAI)几方面的变化同时观察副反应,并通过检测清晨皮质醇浓度来客观评价HD对肾上腺皮质的抑制作用 采用HPLC测定HD灌肠后不同时间血及肠粘膜活检组织中的该药浓度 结果:两组在临床症状,结肠镜下,组织学及DAI进步方面(?)L显著性差异(P>0.05)HD组2例出现颜面及双下肢水肿.而BUD组无此副反应:清晨皮质醇浓度变化两组有显著性差异(P<0.05)测出两例UC患者使用HD灌肠后粘膜及血中的药代学参数 结论:BUD和HD灌肠治疗(?)段UC临床疗效相当,前者副反应小 HD局部灌肠可能有部分全身作用     

Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis

BACKGROUND: Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether budesonide enema, 2 mg/100 ml, administered twice daily (b.i.d.) could increase the remission rate in comparison with the once daily (o.d.) standard regimen. Furthermore, we evaluated whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect. METHODS: 149 patients with active distal UC were treated in a controlled, double-blind multicentre study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse. RESULTS: The remission rates at 4 weeks were 33% for o.d. and 41% for b.i.d. regimens (NS) and correspondingly 51% and 54% at 8 weeks (NS). The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% (P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS). CONCLUSION: Budesonide enema 2 mg o.d. appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.     

Effect of Budesonide Enema on Remission and Relapse Rate in Distal Ulcerative Colitis and Proctitis

Background: Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether budesonide enema, 2 mg/100 ml, administered twice daily (b.i.d.) could increase the remission rate in comparison with the once daily (o.d.) standard regimen. Furthermore, we evaluated whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect. Methods: 149 patients with active distal UC were treated in a controlled, double-blind multicentre study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse. Results: The remission rates at 4 weeks were 33% for o.d. and 41% for b.i.d. regimens (NS) and correspondingly 51% and 54% at 8 weeks (NS). The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% ( P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS). Conclusion: Budesonide enema 2 mg o.d. appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.     

A clinical trial of combined use of rosiglitazone and 5-aminosalicylate for ulcerative colitis

AIM： To investigate the therapeutic effects of the combined use of rosiglitazone and aminosalicylate on mild or moderately active ulcerative colitis （UC）. METHODS： According to the national guideline for diagnosis and treatment of inflammatory bowel disease （IBD/ in China, patients with mild or moderately active UC in our hospital were selected from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure and those who had received corticosteroid or immunosuppressant treatment within the last month were excluded. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group （TG/ with rosiglitazone 4 mg/d plus 5-ASA 2 g/d daily or the control group （CG/with 5-ASA 2 g/d alone, respectively, for 4 wk. Clinical changes were evaluated by Mayo scoring system and histological changes by Truelove-Richards＇ grading system at initial and final point of treatment. RESULTS： Forty-two patients completed the trial, 21 each in TG and CG. The Mayo scores in TG at initial and final points were 5.87 （range： 4.29-7.43/ and 1.86 （range： 1.03-2.69/ and those in CG were 6.05 （range： 4.97-7.13/and 2.57 （range： 1.92-3.22/respectively. The decrements of Mayo scores were 4.01 in TG and 3.48 in CG, with a remission rate of 71.4% in TG and 57.1% in CG, respectively. Along with the improvement of disease activity index （DAI/, the histological grade improvement was more significant in TG than in CG （P 〈 0.05/. CONCLUSION： Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. Rosiglitazone can alleviate colonic inflammation which hopefully becomes a novel agent for UC treatment.     

Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.

5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.     

5-ASA in ulcerative colitis： Improving treatment compliance

5-aminosalicylic acid （5-ASA） compounds are a highly effective treatment for ulcerative colitis （UC）. While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix （MMx） is a novel, high strength （1.2 g）, oral formulation designed for oncedaily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA （Asacol）, even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.     

Management of distal ulcerative colitis: frequently asked questions analysis

The majority of patients with ulcerative colitis have disease involving only the distal colon. Although 5-aminosalicylic acid (5-ASA, mesalazine) and corticosteroids remain the important drugs used in the management of distal colitis and proctitis, recent expansion of delivery options of 5-ASA and high level evidence regarding efficacy have led to a shift in treatment strategies. The availability of 5-ASA in enema, foam and suppository formulations has enabled optimization of delivery of 5-ASA to the affected mucosa. Such therapy has superior efficacy and fewer adverse effects compared with those of topical corticosteroids. Furthermore, rectal delivery is effective in the maintenance of remission. Consequently, new guidelines for the management of distal colitis have focussed more on rectal delivery and on optimizing 5-ASA dosage than previously. However, corticosteroids remain an important remission-inducing agent, and immune-modulating drugs play a clear role in prevention of relapse and in managing chronically active disease. The changes in guidelines have raised several management questions, many of which are addressed in this review.     

Double-blind,placebo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using<Superscript>99m</Superscript>Tc-labeled 5-ASA suppositories

Patients with active distal proctitis received either 5-aminosalicylic (5-ASA) acid or identical placebo suppositories, 500mg t.i.d. for 6 weeks. Activity at 3 and 6 wks was assessed using a Disease Activity Index (DAI), derived from four categories: number of daily evacuations more than usual, evacuations containing blood, sigmoidoscopy appearance, and physician's overall assessment. Each category was graded 0–3. There was thus 0–12 points scored ranging from complete remission to severe disease. A minimum score of 3 from two categories was necessary for study entry. Of 27 patients randomized, 14 received active medication and 13 placebo. Of the 14 patients, with initial mean DAI 7.1 ±1.8, 11 were in complete remission at 6 wks (78.6%). Whereas, there was no significant change in the placebo group, with initial mean DAI 7.1±1.8. An additional 6 patients with inflammatory bowel disease and 6 healthy volunteers were given^99mTc-labelled 5-aminosalicylic acid suppositories. The extent of spread was limited to the rectum, and the suppositories were retained for 3 hours. There was no absorbed radioactivity. 5-ASA suppositories are safe, well-tolerated, and effective treatment for active distal proctitis.     

益生菌对重度溃疡性结肠炎辅助治疗作用的临床研究

目的观察益生菌(双歧三联活菌)对重度溃疡性结肠炎(UC)的治疗作用和安全性。方法采用随机对照设计,将26例重度UC患者分为实验组13例和对照组13例,两组均先给予常规糖皮质激素及抗生素治疗1周,之后治疗组给予美沙拉嗪联合双歧三联活菌胶囊,对照组仅给予美沙拉嗪治疗,疗程均为8周。对两组患者治疗前后临床症状总积分降低百分比、疾病活动指数(DAI)、肠镜分级、病理组织学分级变化进行比较。结果两组组内治疗前后比较:临床症状总积分降低百分比,治疗组为显效,对照组为有效;实验组治疗前后DAI、肠镜分级、病理组织学分级变化差异均具有统计学意义;对照组治疗前后DAI变化差异有统计学意义,肠镜分级、病理组织学分级变化差异均无统计学意义。治疗后两组间比较:实验组与对照组临床症状总积分降低百分比分别为(68.580±16.780)%和(47.760±18.850)%,差异具有统计学意义(P<0.01);DAI变化差值分别为3.900±1.021和2.100±0.961,差异具有统计学意义(P<0.001);肠镜分级积分变化差值分别为1.200±0.687和0.500±0.405,差异具有统计学意义(P<0.01);病理组织学分级积分变化差值分别为1.000±0.581和0.400±0.228,差异具有统计学意义(P<0.01)。结论美沙拉嗪联合益生菌治疗重度UC的临床疗效优于单用美沙拉嗪,且有较好的安全性,具有临床推广价值。     

二丙酸倍氯米松和传统糖皮质激素灌肠治疗溃疡性结肠炎:Meta分析

目的系统评价二丙酸倍氯米松(beclomethasone dipropionate,BDP)和传统糖皮质激素(traditional glucocorticosteroids,TGC)灌肠治疗溃疡性结肠炎(culcerative colitis,UC)的有效性及安全性。方法计算机检索PubMed、EBSCO、The Cochrane Library、CBM、CNKI数据库发表的有关UC患者BDP灌肠和TGC灌肠的随机对照试验。2名评价者独立对纳入文献进行质量评价和数据提取,采用RevMan 5.1进行数据分析。结果共纳入6篇研究共计351例患者,其中BDP组181例、TGC组170例。Meta分析结果显示:灌肠治疗后两组在内镜(OR=0.60,95%CI:0.17~2.17)及临床症状(OR=1.00,95%CI:0.32~3.11)改善方面差异无统计学意义(P0.05);BDP对病理组织学改善优于TGC(OR=0.33,95%CI:0.12~0.95,P=0.04);灌肠治疗后两组的空腹皮质醇浓度(MD=0.28,95%CI:0.09~0.48,P=0.004)及ACTH兴奋试验(MD=0.57,95%CI:0.29~0.84,P0.01)差异有显著统计学意义。结论 BDP灌肠治疗UC优于TGC。     

A new oral delivery system for 5-ASA: preliminary clinical findings for MMx

BACKGROUND: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. METHODS: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index < or =4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. RESULTS: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, -12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. CONCLUSIONS: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis.     

Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis

Oral aminosalicylates such as sulfasalazine and mesalamine are widely prescribed for the treatment of mild or moderately active distal ulcerative colitis. However, a critical review of the literature demonstrates that rectal 5-aminosalicylic acid (5-ASA) is the optimal therapy for this disease. Meta-analyses of published trials show that rectally delivered 5-ASA is superior to placebo and to conventional rectal corticosteroids in inducing remission of distal ulcerative colitis, whereas the combination of rectal 5-ASA with a rectal corticosteroid or oral aminosalicylate is superior to rectal 5-ASA alone. For maintaining remission of distal ulcerative colitis, rectal 5-ASA is significantly better than placebo and at least as effective as oral 5-ASA. The dosage forms available for rectal delivery include suppositories, foams, and liquid enemas, and selection among these preparations should be guided by the proximal extent of disease and patient preference. The efficacy of rectal 5-ASA is complemented by its low rate of reported adverse effects, which may reflect its reduced potential for systemic absorption. This review summarizes the evidence supporting the role of rectal 5-ASA as a first-line therapy for mild or moderately active distal ulcerative colitis, and offers guidelines for its use.     

Recent advances in the management of distal ulcerative colitis

The most frequent localization of ulcerative colitis (UC) is the distal colon. In treating patients with active distal UC, efficacy and targeting of the drug to the distal colon are key priorities. Oral and rectal 5-aminosalicylic acid (5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment. It has been reported that many UC patients are not adherent to therapy and that non-compliant patients had a 5-fold risk of experiencing a relapse. These findings led to the introduction of once-daily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence. New formulations of mesalazine, including the multi-matrix delivery system, and mesalazine granules, which allow once-daily administration, have been developed. They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials. However, existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations. It seems that the new formulations are at least as effective as classical oral 5-ASA formulations. Other treatment options, in the case that 5-ASA therapy is not effective, include systemic corticosteroids, thiopurines (azathioprine or 6-mercaptopurine), cyclosporine, infliximab and surgery. The combination of a prompt diagnostic work-up, a correct therapeutic approach and an appropriate follow-up schedule is important in the management of patients with distal UC. This approach can shorten the duration of symptoms, induce a prolonged remission, improve patient's quality of life, and optimize the use of health resources.     

5-Aminosalicylic acid enemas in patients with active ulcerative colitis. Influence of acidity on the kinetic pattern

Enemas containing 1000 mg 5-ASA were administered to patients with active distal colitis in three separate studies: as a single dose in a neutral solution (pH 7.4); as a single dose in a slightly acidic, buffered suspension (pH 4.8); and as multiple doses once a day for 10 days with the acidic enema. 5-ASA was relatively rapidly absorbed from the neutral solution, resulting in plasma concentrations of 5-ASA sometimes two to three times higher than those found after peroral salazosulphapyridine (SASP) treatment. In contrast, absorption from the acidic enema was reduced and/or prolonged, giving plasma concentrations similar to those found during oral SASP treatment. After repeated doses of the acidic enema, plasma concentrations after an enema resembled those seen after the single dose. Urinary excretion was significantly lower, suggesting a reduced fraction of absorption at steady-state conditions. No side effects were observed, and no local irritation was reported. An acidic buffer suspension with 5-ASA seems to be safe for use as enema and deserves further clinical testing for treatment of distal ulcerative colitis.     

5-Aminosalicylic Acid Enemas in Patients with Active Ulcerative Colitis

Enemas containing 1000 mg 5-ASA were administered to patients with active distal colitis in three separate studies: as a single dose in a neutral solution (pH 7.4); as a single dose in a slightly acidic, buffered suspension (pH 4.8); and as multiple doses once a day for 10 days with the acidic enema. 5-ASA was relatively rapidly absorbed from the neutral solution, resulting in plasma concentrations of 5-ASA sometimes two to three times higher than those found after peroral salazosulfapyridine (SASP) treatment. In contrast, absorption from the acidic enema was reduced and/or prolonged, giving plasma concentrations similar to those found during oral SASP treatment. After repeated doses of the acidic enema, plasma concentrations after an enema resembled those seen after the single dose. Urinary excretion was significantly lower, suggesting a reduced fraction of absorption at steady-state conditions. No side effects were observed, and no local irritation was reported. An acidic buffer suspension with 5-ASA seems to be safe for use as enema and deserves further clinical testing for treatment of distal ulcerative colitis.