Effect of combination of antacid and cimetidine on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer

By means of a Latin square design, the effect of antacid alone and in combination with cimetidine on a 24-hour intragastric hydrogen ion (H+) activity and serum gastrin profiles was studied in eight patients with duodenal ulcer. Antacid given seven times a day (one and three hours after meals and at bedtime) combined with 600 mg BID of cimetidine (C + A7) achieved greater suppression of H+ after breakfast, overnight, and over the 24-hour period than did antacid alone seven times daily (A7). Antacid given four times a day (one and three hours after lunch and after supper) combined with cimetidine BID (C + A4) maintained the neutralizing capacity during this time, but was less effective than the C + A7 regimen. However, C + A4 produced more suppression of nocturnal H+ than did A7. A higher percentage of the readings at or above pH 4.0 were obtained with C + A7 than with A7 or C + A4. A greater postprandial integrated gastrin response was obtained with all active treatments as compared with a placebo regimen. The mean peak cimetidine concentration (Cmax) was higher but the time to peak (Tmax) was shorter after the morning than after the evening dose. The area under the cimetidine concentration-time curve and the Cmax and Tmax values after the morning and evening doses of cimetidine were not affected by the coadministration of antacid. In conclusion: (1) combination therapy of cimetidine plus antacid is more effective than antacid alone in the reduction of intragastric H+; (2) antacid alone fails to suppress the overnight intragastric acidity; and (3) antacid given concurrently with cimetidine does not interfere with pharmacokinetic determinants of plasma cimetidine concentration.     

Pathogenesis and therapy of gastric and duodenal ulcer disease

Despite the decreasing frequency of Helicobacter pylori-induced peptic ulcers, peptic ulcer disease remains a major clinical problem partly because nonsteroidal anti-inflammatory drug ulcers have increased in frequency. The reduction in nonsteroidal anti-inflammatory drug ulcers by use of selective cyclooxygenase-2 inhibitors will not eliminate the problem because of increased use of aspirin for cardiovascular prophylaxis. This article reviews current concepts of peptic ulcer pathogenesis and therapy according to ulcer etiology; discusses potential interactions between etiologies; and considers the therapy for H pylori infection including the effects of antimicrobial resistance, and the role of bismuth quadruple therapy or furazolidone salvage therapy.     

Pharmacokinetic study of cimetidine in pediatric duodenal ulcer

The subjects were five schoolboys aged 7 to 12 years with endoscopically proved duodenal ulcers. After the oral administration of 10 mg/kg of cimetidine, the mean peak cimetidine level was 2.86 microgram/ml; the time to peak level was 1.3 hours; the area under the concentration-time curve was 9.74 microgram/ml.hr; the elimination half-life was 1.55 hours; and 56% of the drug was excreted unchanged in the urine. The plasma cimetidine level remained above 1.0 microgram/ml for 3.4 hours and above 0.5 microgram/ml for 5.8 hours. Gastric pH was increased to 5 or above for three to six hours. These results are similar to those reported previously in other pediatric patients. After eight weeks of treatment with 20 mg/kg of cimetidine daily, the duodenal ulcers were completely healed in four of five patients studied.     

Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.     

Acute effects of antacids on gastric juice components in duodenal ulcer patients

In 10 duodenal ulcer patients gastric juice was aspirated every 10 min for 20 min before and 200 min after sham feeding. One antacid tablet or placebo was given 80 min after the sham feeding. Analyses of the aspirates showed that antacids reduced mean hydrogen ion activity and pepsin concentration significantly for 40 and 60 min, respectively, and increased phospholipid concentration for 30 min, compared with placebo. Highest mean pH was 2.52. The percentage of pH readings at or above pH levels of 2, 3, and 4 during the 2 h period following antacid administration was 29, 10, and 2%, respectively. No significant differences between antacid and placebo were found regarding intragastric concentrations of bile acids and prostaglandin E2. When one antacid tablet was administered 80 min after a real meal, the effect on intragastric pH was similarly weak, but lasted slightly longer. Acid neutralization' alone can hardly explain the ulcer-healing effect of low-dose antacids. Antacid-induced increase in intragastric concentration of phospholipids is a new and potentially important observation.     

Efficacy of once-daily cimetidine in preventing recurrence of duodenal ulcer

In a prospective multicenter trial, 88 patients with acute duodenal ulcers that were healed with ranitidine were randomly assigned to receive maintenance treatment with either cimetidine 400 mg (n = 45) or placebo (n = 43) at bedtime for six months. Ten percent of the patients experienced moderate or severe pain both during the day and at night while on placebo during the maintenance phase. The average proportion of cimetidine patients experiencing moderate or severe pain during the day or night was 50% and 80% lower than placebo, respectively. Ulcer-like symptoms prompted endoscopy in 44% (19 of 43) of the placebo patients compared with 18% (eight of 45) of patients receiving cimetidine (P = 0.009). At the completion of the maintenance study, cumulative symptomatic ulcer recurrence rates were 28% (12 of 43) for those on placebo compared with 13% (six of 45) for cimetidine patients. The adverse drug effects noted were similar between treatment groups, with no unexpected reactions reported. A low dose of cimetidine (400 mg) at bedtime effectively reduced the incidence of gastrointestinal symptoms that were severe enough to prompt endoscopy as well as the actual recurrence of ulcers in those patients who had responded to initial therapy with ranitidine, but who continued to be at increased risk of reulceration.     

Plasma fibronectin in gastric and duodenal ulcer

Solid phase enzyme immunoassay was made to measure fibronectin in blood plasma of 132 patients with ulcer and healthy controls. Exacerbations of ulcer occurred in a significant lowering of fibronectin concentration which tended to an increase with ulcer healing. In the scarring phase fibronectin levels returned to normal. A local stimulating action of a plasma fibronectin preparation on scarring of the ulcer defect is validated.     

An evaluation of cimetidine and ranitidine in the pain relief and acute healing of duodenal ulcer disease

In a multicenter, single-blind, randomized trial, the effectiveness in pain relief and healing of three regimens of H2-receptor antagonists was compared in 338 patients with endoscopically confirmed active duodenal ulcers, 112 receiving cimetidine 300 mg four times daily (QID), 110 receiving cimetidine 800 mg at bedtime (HS), and 116 receiving ranitidine 300 mg HS. Evaluation of the immediate symptomatic response during the first 24 hours of therapy showed that a greater proportion of patients with nighttime pain were improved on HS regimen and a greater portion of patients with daytime pain were improved on QID regimen. With continued treatment the differences between a once-daily and a four-times-daily regimen disappeared and the HS regimen provided as much daytime pain relief as the QID regimen. For the two once-daily regimens where ranitidine and cimetidine were directly compared, a greater proportion of patients on cimetidine 800 mg HS had an immediate symptomatic improvement than on ranitidine 300 mg HS. When those who smoked were evaluated separately this difference was also evident. During the first 24 hours, a total of 68% of the smokers in the cimetidine HS treatment groups had improvement in daytime pain versus 44% of patients in the ranitidine group at day one. Nighttime pain relief in smokers on day one was apparent in 78% of the patients receiving the cimetidine HS regimen, in contrast to 67% of ranitidine-HS-treated patients. At the completion of a four-week course of treatment, both physicians' and patients' global assessments of the reduction in the severity and frequency of ulcer-related symptoms significantly favored cimetidine HS over ranitidine HS. These results after four weeks of treatment were corroborated by the endoscopy data, which showed 71% of patients in the cimetidine HS group were healed, compared with 63% in the ranitidine HS group. The 300 mg QID cimetidine regimen produced a 69% healing rate. For those patients whose ulcers were unhealed by the end of four weeks of treatment, a further course of treatment produced almost 9C% healing in all treatment groups and symptomatic relief in virtually all patients. None of the regimens was associated with unexpected adverse effects and all patients tolerated the treatments well. The results of this study confirm the efficacy and safety of single bedtime doses of cimetidine or ranitidine, as well as the four-times-daily cimetidine regimen, in the acute treatment of duodenal ulcers.(ABSTRACT TRUNCATED AT 400 WORDS)