A double-blind study of misoprostol (SC-29333) in the healing of duodenal ulcer

In a double-blind randomized placebo controlled trial, 50 patients with endoscopically confirmed duodenal ulcer were treated with either misoprostol 200 micrograms or placebo in q.i.d. doses for 4-8 weeks. Of 25 patients in the placebo group, four defaulted and two were withdrawn due to worsening of symptoms. Of 25 misoprostol-treated cases, 17 cases (68%) and 21 cases (84%) healed at 4 and 8 weeks respectively, compared with three (14%) and five (24%) of the 21 placebo-treated cases (P less than 0.001). Except for diarrhoea in 2 patients in each group and itching in one with misoprostol, no serious side effects were noted.     

Prevention of duodenal ulcer recurrence by pirenzepine 50 mg twice daily

Eighty-four patients with healed duodenal ulcers were treated for 1 year with pirenzepine, 50 mg twice daily, or placebo in this double-blind, randomized, multicenter trial. Clinical follow-up and endoscopy were performed before and after 3, 6, and 12 months of treatment. Endoscopy was also carried out whenever symptoms compatible with ulcer recurrence were present for more than 2 days. Both groups were well matched for age, sex, duration of peptic ulcer disease, and smoking habits. There were 21 drop-outs due to lack of compliance. Therefore, 32 patients treated with pirenzepine and 31 with placebo were included in the analysis. Expressed in cumulative percentage of recurrence, with pirenzepine, 28% of the patients had a relapse at 3 months, 41% at 6 months, and 53% at 12 months; with placebo, the recurrence rates were 58% at 3 months, 68% at 6 months, and 71% at 12 months. The mean success time at 1 year is also longer for pirenzepine (7.38 months) than for placebo (5.52 months). These differences are significantly in favor of pirenzepine (p less than 0.05). Both treatments were well tolerated. Dry mouth was more frequently observed with pirenzepine (14 versus 5 patients). We conclude that pirenzepine, 50 mg twice daily, significantly reduces the relapse rate of duodenal ulcers during a 1-year maintenance treatment.     

A comparison of sucralfate dosage schedule in duodenal ulcer healing. Two grams twice a day versus one gram four times a day

The conventional dosage schedule for sucralfate is 1 g 4 i.d., but a dose of 2 g 2 i.d. may be equally effective in duodenal ulcer healing. We compared the efficacy of these two regimens in duodenal ulcer healing. Seventy-seven patients with endoscopically proven duodenal ulceration were entered into a double-blind, controlled study and randomized to treatment with sucralfate 2 g 2 i.d. (on waking and at bedtime) or 1 g 4 i.d. (1/2 h before meals and at bedtime). The patients were endoscoped before entry into the study, after 4 weeks, and after 8 weeks if unhealed at 4 weeks. Of the patients considered suitable for analysis at 4 weeks, 79% (26/33) of those taking 2 g 2 i.d. had healed ulcers in comparison to 72% (23/32) of those taking 1 g 4 i.d. After 8 weeks, cumulative healing rates were 85% (28/33) and 80% (24/30), respectively. The results suggest that the more convenient dosage schedule of 2 g 2 i.d. is as effective as the 1 g 4 i.d. regimen in the short-term treatment of duodenal ulcer.     

A comparison of two prostaglandin analogues (enprostil vs misoprostol) in the treatment of acute duodenal ulcer disease

We conducted a clinical trial to compare the efficacy and safety profile of two prostaglandin analogues, enprostil (35 μg twice daily) and misoprostol (200 μg four times daily) in the treatment of acute duodenal ulcers in 214 patients. The two agents healed approximately 80% and in excess of 90% of duodenal ulcers after 4 and 6 weeks' therapy, respectively. There was a significantly lower ulcer healing rate in both treatment groups in smokers compared with nonsmokers (P<0.05). However, daytime and nighttime ulcer pain relief was achieved in fewer than 50% of patients by either agent. Diarrhea, which occurred in more than 40% of patients, was the predominant side effect, and occurred mainly during the first 2 weeks of therapy with either agent. Nevertheless, this side effect was mild and self-limiting in the majority of patients. Both agents were found to be safe and well tolerated by the majority of patients. We conclude that these prostaglandin analogues are safe and effective duodenal ulcer healing agents. Furthermore, there was very little difference between enprostil and misoprostol. The limiting factors, however, for their routine use as ulcer healing agents are their low efficacy with regard to ulcer pain relief and the high incidence of diarrhea.     

Low-dose cimetidine in the acute treatment of duodenal ulcer. Comparison of a single nocturnal dose regimen with a twice daily regimen

A 0.5 g daily dose of cimetidine was as effective as a 1 g dose in the acute treatment of duodenal ulcer patients in Hong Kong. The aims of the present study were, first, to determine whether low-dose cimetidine treatment was as effective as standard doses in acute duodenal ulcer treatment of patients in Singapore, and second, to compare a single nocturnal dosage regimen with a twice daily regimen. In this single centre, double-blind, controlled trial, 282 patients with endoscopically proven duodenal ulcer were randomized to receive four weeks' treatment with cimetidine using one of three dosage regimens: (A) 800 mg at night; (B) 400 mg at night; or (C) 400 mg twice daily. Two hundred and forty-seven patients were evaluated. The incidences of healing at four weeks were: (A) 40/80 (50%), (B) 39/88 (44%); and (C) 48/79 (61%); (B vs C: P less than 0.05; A vs C: NS; 95% confidence limits: -5% to 27%; A vs B: NS, 95% confidence limits: -6% to 21%). Of 183 patients who had antral biopsies taken, 176 (96%) had histological gastritis, while 167 (91%) were positive for Helicobacter-like organisms. The occurrence of gastritis or Helicobacter-like organisms had no influence on ulcer healing. A 400 mg dose of cimetidine is therefore suboptimal for the treatment of duodenal ulcer in patients in Singapore. A single nocturnal dosage regimen may be less effective than a twice daily regimen.     

Comparison of sucralfate and ranitidine twice daily in duodenal ulcer treatment: a multicenter randomized double-blind study

Sucralfate and ranitidine were compared in the treatment of duodenal ulcer in this multicenter, randomized, double-blind study. A total of 165 patients with endoscopically proven duodenal ulceration were included in the trial and randomized to treatment with sucralfate, 2 g b.i.d. (morning and evening with an empty stomach), or ranitidine, 150 mg twice daily. All patients were endoscopically examined after 4 and, if unhealed, 8 weeks. Of the patients considered suitable for analysis at 4 weeks, 73.5% (61 of 83) of the sucralfate group demonstrated healing of the ulcer in comparison with 63.3% (50 of 79) of the ranitidine group. At 8 weeks cumulative healing rates were 89% (74 of 83) and 84.8% (67 of 79), respectively. When smokers were considered separately, healing rates at 4 weeks were 69.2% (36 of 52) for sucralfate and 53.3% (24 of 45) for ranitidine. At 8 weeks cumulative healing rates were 92.3% (48 of 52) and 77.7% (35 of 45), respectively (p less than 0.05). Overall, there was no difference in the two groups regarding symptom relief and side effects. These results suggest that these drugs are equally effective in the short-term treatment of duodenal ulcer, although in smokers sucralfate appears to be more effective than ranitidine.     

Factors influencing healing of duodenal ulcer

To study the efficacy of a single bedtime dose of H₂-receptor antagonist in the healing of duodenal ulcer, a 12-week randomized double-blind controlled trial of oxmetidine, which is equipotent to cimetidine and has a similar duration of action, was performed in 80 patients. Oxmetidine, 600 mg bedtime, resulted in significantly more complete healing than placebo at weeks 2, 4, 6, 8, 10, and 12 as assessed endoscopically. At weeks 4 and 6, 72.5% and 85%, respectively, of ulcers were completely healed by oxmetidine, and 36.8% and 41.7%, respectively, by placebo. Of 45 prospectively obtained patient characteristics, high pentagastrin-stimulated maximal acid output and large ulcer diameter significantly affected healing adversely. These results indicate that duodenal ulcer healing may be achieved by reducing the nocturnal acid secretion alone.Part of work presented at American Gastroenterological Association Annual Meeting, May 23–25, 1983, Washington D. C. Supported by University Research Grants (041.0006, 041.0009) and Wing Lung Bank Medical Research Fund (311/030/8009/31), University of Hong Kong.     

Omeprazole versus placebo in duodenal ulcer healing

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A per protocol analysis of healing rates showed a significant advantage for omeprazole (P<0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P<0.01) in the omeprazole group. All-patients treated analyses for healing and pain relief gave results similar to the respective per protocol analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (>150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml). Observations from Europe and Australia of >90% healing of duodenal ulcers after four weeks of omeprazole therapy were not confirmed in this study. No single factor explains this difference. Considerable variation in the degree of suppression of acid secretion has been demonstrated with the 20-mg daily dose of omeprazole; it is possible that, in US populations, a greater degree of antisecretory effect may be required to achieve the healing rates observed in Europe and Australia. In conclusion, omeprazole was more effective than placebo in the treatment of active duodenal ulcer, as determined by ulcer healing and relief of pain, and was well tolerated in the short-term treatment of patients with duodenal ulcer.     

20 versus 30 mg omeprazole once daily: effect on healing rates in 115 duodenal ulcer patients

In a double-blind, dose comparison multicenter trial 115 patients with duodenal ulcer were treated with either 20 or 30 mg oral omeprazole once daily for 4 weeks. There was no difference in the healing rates for the two groups after 2 and 4 weeks. After 2 weeks with 20 and 30 mg healing frequencies were 79.0 and 72.7%, after 4 weeks 96.5 and 92.7%. No difference was observed between the groups in the number of pain episodes during day and night. No side effects to the drug occurred. A daily dose of 20 mg omeprazole may be effective in ulcer therapy.     

A single-centre study of gastric ulcer healing with 300 mg ranitidine at night versus 150 mg ranitidine twice daily

In a single-centre study 59 patients with gastric ulcer were treated either with 300 mg ranitidine at night or with 150 mg ranitidine twice daily. After 4 and 8 weeks 73% and 97%, respectively, of those treated with 300 mg at night and 59% and 86% of those treated with 150 mg twice daily had complete ulcer healing. These differences between the two groups were not statistically significant. No serious side effects were seen. Ranitidine, 300 mg at night, appears to be at least as effective as the standard 150 mg twice daily regimen in the treatment of gastric ulcer.     

Effects of misoprostol on delayed ulcer healing induced by aspirin

Clinical studies have suggested that treatment with the prostaglandin E₁ analog, misoprostol, leads to significant healing of ulcers in patients taking regular nonsteroidal antiinflammatory therapy. This study aimed to investigate mechanisms involved in this healing using a rat model. Gastric ulcers were induced by application of acetic acid using a standard technique. Rats were treated with 200 mg/kg aspirin, 100 µg/kg misoprostol, a combination of both treatments, or methylcellulose vehicle for up to two weeks, starting two days after ulcer induction. Ulcers were assessed by macroscopic measurements of area and by quantitative histological measurements. Aspirin delayed ulcer healing compared with controls, while misoprostol significantly reversed this effect. Quantitative histology revealed that misoprostol cotreatment significantly increased mucosal regeneration compared with aspirin treatment alone. However, misoprostol did not reverse the effects of aspirin on an index of wound contraction. We conclude that treatment with misoprostol significantly reverses the delayed healing effect of aspirin, and this may occur via an effect on epithelial regeneration.This study was supported by a grant from the Alfred Hospital Medical Research Advisory Committee.     

Effect of misoprostol and antacids on gastric and duodenal mucosal enzyme activities in duodenal ulcer patients

The activities of 11 marker enzymes from the gastric and duodenal mucosa were determined in 15 patients with active duodenal ulcer disease before therapy, after 4 weeks of therapy with the prostaglandin E1 analogue misoprostol, 400 micrograms twice daily, and after another 4 weeks without any therapy. Another 15 patients were given a high-dose liquid antacid regimen. The activities were measured in homogenized material obtained with forceps through an endoscope. The healing rates of the two groups at 4 weeks were 53% and 80%, respectively. No changes in mucosal inflammation were noted during therapy. During treatment with misoprostol the activities in the descending duodenum of the membrane enzymes alkaline phosphatase, leucyl-beta-naphthylamidase, gamma-glutamyltransferase, and 5'-nucleotidase increased towards the values seen in normal controls. Despite a higher healing rate, no changes in the enzyme activities occurred in the group given high-dose antacid therapy. Four weeks after cessation of therapy the enzyme activities in the misoprostol group were not significantly different from the pretreatment values. In the biopsy specimens from the duodenal bulb the activities of monoamine oxidase fell during treatment with misoprostol and were restored to the pretreatment activity when therapy was stopped. In the stomach mucosa the enzyme activities were largely unchanged during treatment with both misoprostol and antacids. These results indicate that misoprostol and antacids have different mechanisms of action but may also suggest that the demonstrated enzymic changes are unrelated to the healing process.     

Pharmacokinetic analysis of amikacin twice and single daily dosage in immunocompromised pediatric patients

Summary Ten children received amikacin twice daily and 13 were treated using the single daily protocol. All had fever and neutropenia on admission, and received a total daily dose of 20 mg/kg when included in the study. Individual pharmacokinetic parameters were calculated using a one-compartment model for two blood amikacin samples. The mean (±SD) of elimination half-life (h), amikacin clearance (l/h/kg), volume of distribution (l/kg), peak concentration (μg/ml) and trough concentration (μg/ml) were: 2.51 (0.74) and 2.85 (0.32) h; 0.26 (0.16) and 0.115 (0.02) l/h/kg; 0.74 (0.44) and 0.47 (0.11) l/kg; 19.1 (12.3) and 42.6 (12.6) μg/ml; 0.85 (0.74) and 0.18 (0.24) μg/ml with twice and single daily dosage schedules, respectively. A single daily dose of amikacin had a significantly longer elimination half-life, lower clearance, higher peak concentration and lower trough concentration in comparison to the twice-daily schedule. The use of amikacin 20 mg/kg daily delivered in a single daily dose is recommended for immunocompromised pediatric patients with fever and neutropenia, in spite of the measured pharmacokinetic differences. Part of this work was presented in a poster session at the 8th International Congress on Anti-Cancer Treatment, Paris, France, February 1998.     

愈疡止痛煎剂对十二指肠溃疡大鼠溃疡愈合质量的影响

[目的]探讨愈疡止痛(YYZT)煎剂对实验性大鼠十二指肠溃疡(DU)愈合质量的影响.[方法]用L-半胱胺酸盐酸盐复制大鼠DU模型,设立空白对照(A)组、病理模型(B)组、YYZT(C)组、雷尼替丁(D)组.3周后处死动物,观察溃疡愈合程度并评价溃疡愈合质量,测定胃液pH值及血清表皮生长因子(EGF)水平.[结果]C组胃酸较其余各组均降低(P＜0.05);C组胃液pH值及血清EGF较其余各组明显升高(P＜0.05,＜0.01).[结论]YYZT煎剂在提高溃疡愈合方面有明显优势,其作用机制可能与减少胃酸分泌、升高血清EGF有关.     

Double-blind comparison of two dosage regimens of misoprostol in the treatment of duodenal ulceration

A multicenter double-blind study was conducted in 416 patients (306 male, 110 female) with active endoscopically proven duodenal ulcers who were randomly allocated to receive the prostaglandin E1 methyl ester analog (Misoprostol/Cytotec), either in a dose of 400 micrograms twice daily (206 patients) or 200 micrograms four times daily (210 patients). No significant difference in the healing rates between the two groups was observed at four or eight weeks. In patients treated twice daily, the ulcer healing rate at four weeks for the intent-to-treat cohort was 124/205 (60.5%) and for the evaluable cohort was 96/136 (69.1%). In patients treated four times daily, the healing rate was 124/207 (59.9%) for the intent-to-treat cohort and 96/148 (64.9%) for the evaluable cohort. Similarly, the healing rates achieved at eight weeks for the twice- and the four-times-daily dosages in the intent-to-treat cohort were 72.2% and 74.4%, respectively, and for the evaluable cohort were 88.0% and 86.6%, respectively. Significantly more patients receiving misoprostol twice daily were free of ulcer pain after four weeks of treatment than were those receiving misoprostol four times daily, namely, 71.4% as compared with 57.9%, respectively (P = 0.003) and for a median period of 21 as compared with 17 days (P = 0.002). Diarrhea was more common in patients receiving the drug twice daily, (15.5%) than in those treated four times daily (5%) (P = 0.001). Diarrhea, three or more stools daily, was often transient and self-limiting and only necessitated withdrawal from the trial in nine (4.4%) of those treated with misoprostol twice daily and in one patient (0.5%) of those treated four times daily.(ABSTRACT TRUNCATED AT 250 WORDS)     

Duodenal ulcer healing with four antacid tablets daily

In a double-blind, randomized, multicenter trial in 80 consecutive outpatients with endoscopically verified duodenal ulcer, we have tested the ulcer-healing efficacy of a quite low dose of antacids, given only four times daily. The patients received one chewable aluminum-magnesium-antacid tablet (buffering capacity, 30 mmol/tablet) or placebo 1 h after meals and at bedtime. Re-endoscopy after 4 weeks of treatment showed healed ulcer in 28 of 38 patients (74%) in the antacid group, compared with 11 of 38 patients (29%) in the placebo group (p less than 0.001). The number of days and nights with ulcer pain was significantly less in the antacid group than in the placebo group during the treatment period. Thus, only four antacid tablets a day, with a total buffering capacity of 120 mmol/day, significantly promote duodenal ulcer healing and pain relief.