A Synthetic Prostaglandin E2 Analogue,Enprostil, Hastens Gastric Emptying of Solids in Patients with an Active Duodenal Ulcer

The effect of gastric emptying of two doses (35 and 70μg) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 ± 0.38 min^?1· 10^?2 after placebo to 2.77 ± 0.56 min^?1 · 10^?2 after 35 μg enprostil (p < 0.05 versus placebo) and to 3.65 ± 0.64 min^?1 · 10^?2 after 70 μg enprostil (p < 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 ± 6.9% after placebo, 35.2 ± 7.4% after 35 μ enprostil, and 24.1 ± 8.4% after 70 μg enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

Antisecretory and serum gastrin lowering effect of enprostil in patients with duodenal ulcer disease

This study was designed to compare the effects of enprostil, a synthetic dehydro-prostaglandin E2, on 24-h intragastric pH and serum gastrin profile in patients with duodenal ulcer disease. The dosing regimen included 3 enprostil groups: 35 microgram h.s. (at bedtime), 70 micrograms h.s., and 35 micrograms b.i.d., compared with cimetidine 600 mg b.i.d., and with placebo. Ten patients with inactive duodenal ulcer disease were randomly assigned to all five treatment regimens for 1 wk each according to a Latin Square design. There was a 1-wk washout period between each treatment. Intragastric pH and serum gastrin measurements were carried out on the last day of each treatment week. In placebo-treated patients, intragastric pH rose after each meal and fluctuated between 1.5 and 3.5. Enprostil 35 micrograms b.i.d. and cimetidine elevated pH after breakfast and during the night (p less than 0.05). The single nighttime dose of enprostil had a marked effect on pH only when given in the dose of 70 micrograms and this effect lasted over 13.5 h. The pH values during the night were similar in the groups treated with enprostil 35 micrograms b.i.d. and 70 micrograms h.s. During the daytime, the readings at or above pH 4 were placebo, 5%; cimetidine, 21%; enprostil 35 micrograms b.i.d., 34%. During the nighttime, the readings greater than or equal to 4 were placebo, 12%; cimetidine, 29%; enprostil 35 micrograms b.i.d., 39%; 35 micrograms h.s., 19%, and 70 micrograms h.s., 38%. The postprandial rise in serum gastrin was greatly enhanced by cimetidine, but the change after breakfast was dramatically blunted by enprostil 35 micrograms b.i.d. Gastrin concentration was increased with cimetidine during the night but there was no difference in gastrin concentration overnight between all regimens of enprostil and placebo. This study suggests that (a) enprostil 35 micrograms b.i.d. is as effective as cimetidine 600 mg b.i.d. in suppressing postprandial and nocturnal intragastric acidity; (b) enprostil 35 micrograms b.i.d. and 70 micrograms at night are similarly potent in suppressing nocturnal acidity; and (c) in addition to its cytoprotective effect, enprostil has potent antisecretory and antigastrin properties.     

Gastric emptying of solids, acid secretion and tobacco in duodenal ulcer]

We study in a group of patients with endoscopically diagnosed duodenal ulcer (19; 17 males) and controls (11; 7 males) the gastric emptying of solids through scintigraphy and gastric acid secretion by standard tests. In the same way we investigated prospectively some clinical data, specially smoking habits. As a whole, patients with duodenal ulcer showed an emptying of solids slightly faster than controls (T 1/2-minutes-: 85.4 +/- 28.6 in patients with duodenal ulcer versus 116.9 +/- 46.5 in controls, p less than 0.03). However, most of our patients (15 of 19 or 79%) were found to have a normal emptying rate. No correlation was found between secretory outputs and gastric emptying. Smokers with duodenal ulcer had a faster emptying that non-smokers with duodenal ulcer (T 1/2 74.8 +/- 30.05 vs. 99.91 +/- 19.86; p = 0.05).     

Effect of enprostil, a synthetic prostaglandin E2 on 24 hour intragastric acidity, nocturnal acid and pepsin secretion.

We have studied the effect of a prostaglandin E2 analogue (enprostil), on intragastric acidity, gastric acid and pepsin outputs during a 24 hour period in nine patients with duodenal ulcer in remission. Enprostil 35 micrograms bd dose inhibited 24 hour intragastric acidity by 38% and a 70 micrograms nocturnal dose by 33%. Decrease in nocturnal pepsin secretion was both volume and concentration related.     

Reduction of serum lipoproteins in man by the oral administration of a prostaglandin analogue (enprostil)

Retrospective analysis of ulcer healing trials utilizing enprostil, a synthetic dehydroprostaglandin E2 analogue, has demonstrated a 10% or greater reduction in total serum cholesterol in 64%, 64% and 67%, respectively, of hypercholesterolemic subjects receiving the drug in doses of 70 micrograms, 35 micrograms, and 7 micrograms bid, respectively. Only 16% of subjects receiving placebo exhibited a similar reduction (P less than 0.05). The median percent changes for hypercholesterolemic patients receiving enprostil 70 micrograms, 35 micrograms, or 7 micrograms bid, and placebo were -17%, -13%, -11%, respectively, while the median percent change for those on placebo was 0% (P less than 0.05). Eight normocholesterolemic subjects participated in a double-blind crossover study comparing enprostil 70 micrograms/d with its placebo. Nine days of enprostil administration was associated with reductions in total serum cholesterol (-16%) and apolipoprotein B (-16%) and with significant reductions from baseline for LDL-cholesterol (-22%), the LDL/HDL-cholesterol ratio (-13%), and the ratio of serum apolipoprotein B to apolipoprotein A-1 (-12%). Relative to placebo, mean HDL-cholesterol, total triglycerides, and apolipoprotein A-1 concentrations remained unchanged. Daily oral administration of microgram quantities of enprostil is associated with reductions in total cholesterol, LDL-cholesterol, and apolipoprotein B suggesting therapeutic potential of this synthetic prostaglandin for the treatment of hyperlipidemia.     

Novel approach to quantify duodenogastric reflux in healthy volunteers and in patients with type I gastric ulcer.

A new method is described which allows simultaneous measurement of gastric emptying and duodenogastric reflux and avoids transpyloric intubation. After intragastric instillation of a liquid lipid meal in six healthy volunteers the fractional gastric emptying rate was 2.9 +/- 0.3 in the upright and 2.5 +/- 0.6 SEM X 10(-2)/min in the supine position, respectively (p greater than 0.5). The duodenogastric reflux rate (expressed as fraction of the intraduodenal amount of duodenal marker) was 0.30 (range 0.03-0.81) and 0.22 (0.01-0.55) X 10(-2)/min, respectively (p greater than 0.2). Atropine (40 micrograms/kg) decreased the supine gastric emptying rate to 1.1 +/- 0.2 (p less than 0.05) and increased the supine duodenogastric reflux rate to 2.74 (0.04-9.80) X 10(-2)/min (p less than 0.05). Fasting duodenogastric reflux rate was similar in the supine and upright position, 0.49 (0.04-0.89) and 0.42 (0.06-0.97) X 10(-2)/min, respectively (p greater than 0.5). Fractional gastric emptying rate was similar in 10 volunteers and 17 patients with type I gastric ulcer (2.1 +/- 0.4 vs 1.7 +/- 0.2 SEM X 10(-2)/min, p greater than 0.2). Their duodenogastric reflux rates were also similar, 0.65 (0.01-5.24) vs 1.10 (0.01-10.83) X 10(-2)/min (p greater than 0.5). We conclude therefore that (1) gastric emptying and both fasting and postprandial duodenogastric reflux are independent of the posture; (2) fasting and postprandial reflux are of similar magnitude; (3) atropine shows gastric emptying and increases duodenogastric reflux; and (4) patients with type I gastric ulcer have neither slowed gastric emptying nor increased duodenogastric reflux.     

Effect of calcitonin on gastric emptying in patients with an active duodenal ulcer.

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.     

Effect of enprostil on gastric emptying, intestinal transit time and post-prandial release of gastro-intestinal peptides

The effect of an oral dose of 70 micrograms enprostil (a prostaglandin E2 analogue) on the post-prandial hormone response to a test breakfast was examined in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. Enprostil markedly reduced the post-prandial rises in insulin and glucose-dependent insulinotropic peptide (GIP) but plasma glucose remained unchanged. To study the effects on gut motility 8 healthy volunteers ingested a liquid meal containing 75 g glucose, 20 g lactulose and 99mTc colloid after taking placebo or 70 micrograms enprostil. Gastric emptying, measured using a gamma camera, was unchanged but mouth-to-caecum transit time was significantly longer on enprostil; time to half maximal breath hydrogen: placebo 119 min, enprostil 200 min (p less than 0.05). This delay was associated with a reduced and delayed post-prandial rise in GIP and insulin and with other changes in the gut hormone profile.     

Efficacy and tolerability of enprostil in the treatment of duodenal ulcer. Comparison with cimetidine

Enprostil, a synthetic PGE2, has been shown to have an inhibitory effect on gastric acid secretion, a mucoprotective effect and a postprandial lowering effect on gastrin. A double blind randomized study was performed in 80 patients, in order to evaluate the efficacy and safety enprostil (35 mu b.i.d) as compared to cimetidine (400 mg b.i.d) in duodenal ulcer. Healing rates after two, four and six weeks of treatment, as based on endoscopic evaluation, were 35, 72 and 83 p. 100 for enprostil and 45, 73 and 83 p. 100 for cimetidine, respectively. There were no significant differences between treatment groups. The time to relief of nighttime and daytime ulcer pain and antacid consumption were similar in the two groups. The patient's overall subjective assessment was better in the cimetidine group, but this was not confirmed by physicians' opinions. Diarrhea was observed in 7 p. 100 of patients treated by enprostil compared with 5 p. 100 for patients treated by cimetidine. One enprostil treated patient withdrew from the trial prematurely because of abdominal pain. This study demonstrates the efficacy and safety of enprostil in the treatment of active duodenal ulcer at the dosage of 35 micrograms twice daily.     

Effect of two-week treatment with enprostil (35 μg twice a day) on 24-hour serum gastrin levels

After a meal, a single dose of enprostil, a synthetic dehydroprostaglandin E2, inhibits gastrin level in both normal subjects and patients with duodenal ulcer, whereas H2 blockers exaggerate the postprandial gastrin response. However, the effect of prolonged treatment with enprostil on the gastrin profile is unknown. The aim of this study was to compare serum gastrin levels over a 24-hr period before (day 0) and on the last day (day 14) of a two-week course of enprostil (35 micrograms twice a day). Nine healthy volunteers (four women and five men), ages 29 +/- 5 years (range 23-39) were studied twice during a 24-hr period. Serum gastrin was measured at 30-min intervals during the day and at 2-hr intervals during the night. Enprostil (35 micrograms) was taken after basal gastrin serum measurement at 8:00 AM and PM. Standardized meals were ingested at 8:30 AM, 12:30 PM, and 8:30 PM. The postprandial integrated serum gastrin response was calculated after the three meals (4-hr period). Fasting serum gastrin levels were similar for the two periods. Integrated postprandial gastrin response was significantly inhibited after breakfast and dinner (P less than 0.001). Average results are expressed as mean +/- SEM (pmol/min/liter). During the night, gastrin levels were significantly decreased by enprostil. After 14 days, the inhibition of gastric acid secretion, which induces an increase of gastrin release with other antisecretory drugs, remained counterbalanced by the antigastrin properties of enprostil.     

Influence of smoking on basal and on vagally and maximally stimulated gastric acid and pepsin secretion.

Published data show that smokers have greater basal or peak acid and pepsin outputs, but the mechanisms underlying these effects are unknown. To confirm this and to determine whether these findings extend to, and implicate, any vagal overactivity, gastric secretions collected for 1 h basally, 1 h after 15 min of modified sham feeding (MSF), and 1 h after pentagastrin (6 micrograms/kg subcutaneously) were analyzed for acid and pepsin content in 204 subjects, 104 with duodenal ulcer (66 smokers) and 101 without (57 smokers). Maximal acid outputs (MAO, mu eq/kg/h, means +/- SEM) were higher in smokers than in non-smokers in both duodenal ulcer (DU) (623 +/- 35 versus 491 +/- 35, p less than 0.005) and non-DU (502 +/- 32 versus 376 +/- 20, p less than 0.005). Basal and MSF secretions were generally increased in smokers but, when expressed as a percentage of MAO, were not different in smokers and non-smokers (18% versus 17% and 43% versus 39%, respectively, in DU, and 13% versus 16% and 40% versus 36% in non-DU). Maximal pepsin outputs (units x 10(-2)/kg/h) were also higher in smokers than in non-smokers (DU, 129 +/- 7.9 versus 105 +/- 9.5, p = 0.05, and non-DU, 101 +/- 7.5 versus 77 +/- 10, p = 0.05). Basal and MSF secretions as a percentage of maximal pepsin output were not different in smokers versus non-smokers. Multivariate logistic regression shows that smoking was most strongly associated with MAO and sham feeding outputs, but the duration-intensity (pack-years) of smoking was associated only with elevated MAO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of enprostil on glucose and lipid metabolism in type 2 diabetes

Enprostil, a dehydro-prostaglandin E2 analogue, has been tested as treatment for peptic ulcer. Its effect on blood glucose and lipid metabolism in Type 2 diabetes was assessed in a randomized, double-blind trial. Fifteen patients on sulphonylurea therapy received, in addition, enprostil 35 micrograms or placebo thrice daily for two weeks, with a 2-week wash-out before crossover. Data from 12 patients were analysed. After a 530 Cal test breakfast at the end of active treatment, plasma glucose rose from a fasting concentration similar to that after the last placebo dose (10.5 +/- 0.8 (+/- SE) and 10.6 +/- 1.1 mmol l-1 respectively) to 1, 2 and 3 h concentrations which were 1.5 to 2.1 mmol l-1 lower than on placebo (2 h concentration 14.6 +/- 0.9 vs 16.4 +/- 1.3 mmol l-1, p less than 0.05). Serum fructosamine concentrations at the end of active treatment and placebo were 3.66 +/- 0.22 and 3.78 +/- 0.24 respectively (p = 0.051). No changes in fasting or post-prandial insulin concentrations were observed. After 2 weeks of enprostil, fasting serum triglyceride (1.76 +/- 0.18 mmol l-1) and total cholesterol (6.27 +/- 0.29 mmol l-1) concentrations were lower than after placebo (2.14 +/- 0.25 and 7.35 +/- 0.46 mmol l-1, p = 0.031 and p = 0.002, respectively), the latter effect being primarily due to reduced LDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered solid and liquid gastric emptying in patients with duodenal ulcer disease.

Alteration in gastric emptying has been implicated in duodenal ulcer disease. The precise abnormalities remain controversial. We have used a radionuclide technique to assess solid and liquid gastric emptying in 14 patients with endoscopically proven duodenal ulcer and 22 healthy controls. Solid gastric emptying values for the patient group fell within the normal range. The median time taken for 50% (T50) of the liquid marker to empty from the stomach was 12 minutes (range 6-23 minutes) which was significantly faster (p less than .005) than controls (median 18 minutes, range 11-35). In 10 of the 14 patients, however, the rate of liquid emptying was within the normal range. There was no significant difference in the T50 for gastric emptying of solids between the groups, but in duodenal ulcer patients food left the stomach significantly earlier than in controls (p less than .05). After this, however, the linear rate at which duodenal ulcer patients emptied solid food from the stomach was a median 0.75%/minutes (range 0.5-1.4 minutes), which was slower (p less than .0005) than controls, median 1.25/minutes (range 0.7-2.3). These results show that the pattern of gastric emptying of digestible solids and liquids in patients with duodenal ulcer disease, as a group, is significantly altered.     

ENPROSTIL AND RANITIDINE: COMPARATIVE EFFICACY AND SAFETY IN PATIENTS WITH DUODENAL ULCER

Abstract This randomised, double-blind, double-dummy, multiclinic study of duodenal ulcer healing compared the efficacy and safety of enprostil with ranitidine. The six week trial admitted 164 patients with endoscopically demonstrated duodenal ulcer. Ratings of symptoms and adverse events were collated from patients' daily diaries, and endoscopy was repeated to verify healing after four weeks and, if appropriate, after six weeks. Medication used was enprostil (35 μg capsule) or ranitidine hydrochloride (150 mg tablet) with matching placebos twice daily. After six weeks, 81 % of patients treated with enprostil and 95% of those treated with ranitidine had healed ulcers, a statistically significant difference (p = 0.007). There were no differences between treatment groups for the number of days until the daytime ulcer pain completely ceased. Night-time ulcer pain ceased significantly earlier in the group receiving ranitidine (p = 0.019) and was less severe during the week before the last visit (p = 0.001); daytime pain for ranitidine users was also less severe (p = 0.020) during this week. Mild to moderate adverse experiences were reported by 44% of enprostil and 35% of ranitidine patients. There were no severe adverse events. In conclusion, both enprostil and ranitidine were found to be safe and effective in the treatment of duodenal ulcer. However, the ranitidine regimen used in this trial produced better results than the enprostil regimen.     

Effect of enprostil on amphibian gastroduodenal and human gastric bicarbonate secretion

The protective and ulcer healing properties of prostaglandins are well established. We have explored the possible mode of action of enprostil, a synthetic dehydroprostaglandin E2, on amphibian gastroduodenal mucosal bicarbonate secretion in vitro and on human gastric bicarbonate secretion in vivo. Addition of enprostil (10(-6) M) to the luminal solution of isolated amphibian gastric mucosa produced a 28% increase in bicarbonate secretion without a change in transmucosal potential difference. The same concentration of enprostil added to the luminal solution of isolated amphibian duodenal mucosa produced a 37% increase in bicarbonate secretion and was associated with a rise in transmucosal potential difference. The gastric output of bicarbonate from the human stomach has been calculated using a perfusion technique before, during, and after perfusion with enprostil (35 micrograms) in six healthy volunteers. A significant 78% increase in bicarbonate secretion occurred during the period of enprostil perfusion, falling to normal during the postenprostil period. These changes were caused mainly by an increase in gastric secretory volume with insignificant increases in bicarbonate concentration. These results suggest that stimulation of gastroduodenal bicarbonate secretion by enprostil may play a role in its protective actions.     

Abnormal pattern of gastric emptying of liquid in chronic duodenal ulcer

Gastric emptying was measured in 12 patients with chronic duodenal ulceration and compared with the results from 10 healthy volunteers. The test meal of 300 ml 15% dextrose, labelled with 99mTc-DTPA, was ingested in increments over 6 min. Gamma camera imaging proceeded over 30 min, with a 1-min frame time. A direct correction was applied for the fraction emptying into the small bowel during the ingestion period. Gastric emptying at 6 min was significantly greater in the group with duodenal ulcer (14.4 +/- 2.7% vs. 4.2 +/- 0.9%: mean +/- SEM, p less than 0.01). From this time onwards there were no significant differences in the rates of gastric emptying. These results suggest that chronic duodenal ulcer is associated with an abnormal pattern of gastric emptying of liquid, characterised by an initial rapid phase.     

Inhibitory effect of cigarette smoking on gastric emptying of a solid meal in patients with type I gastric ulcer

The effect of cigarette smoking on gastric emptying (GE) of a radio-labelled solid meal was examined in 14 patients with type I gastric ulcer diagnosed at endoscopy. The patients underwent GE measurement thrice: under basal conditions and for two smoking sessions--without and after cimetidine pretreatment (2 x 400 mg orally for 2 days and 400 mg orally 1.5 h before the isotopic GE examination). Cigarette smoking significantly delayed GE--the median GE index, Ix: 0.688 min-1.10-2 (range 0.033-1.886) after smoking vs. 1.246 min-1.-2 (range 0.384-2.339) under basal conditions, p less than 0.01. The inhibitory effect of smoking on solid GE was blunted when smoking coincided with cimetidine pretreatment--the median Ix amounted to 1.069 min-1.10-2 (range 0.022-1.462) and was not significantly different from that under basal conditions.     

Protective effect of low dose of enprostil against gastric blood loss induced by aspirin in man

This study tested the efficacy of enprostil given both at potent antisecretory (35 micrograms twice daily) and weak antisecretory (7 micrograms twice daily) doses in preventing aspirin-induced gastric blood loss measured chemically in gastric washings in 10 volunteers. Aspirin (500 mg four times a day) increased gastric blood loss compared with placebo (p less than 0.001). When enprostil was given in addition to aspirin, gastric blood loss was not significantly different from basal value. The pH of gastric washings was significantly increased by the large but not by the low dose of enprostil compared with placebo. The two doses of enprostil were equally efficacious, suggesting a mucosal protective effect of enprostil independent of acid inhibition.     

Physiopathological Heterogeneity of the Duodenal Mechanisms that Inhibit Gastric Acid Secretion in Duodenal Ulcer Patients

The effect of duodenal acidification on pentagastrin-stimulated gastric acid secretion was studied in 43 duodenal ulcer patients and in 17 normal controls. Three types of responses were observed: group A, no inhibition of gastric acid secretion occurred in 17 (40%) ulcer patients and in three (18%) controls (p less than 0.05); group B, inhibition of gastric acidity occurred in seven (16%) ulcer patients and in 12 (71%) controls (p less than 0.05), and group C, retarded gastric acid inhibition occurred in 19 (44%) duodenal ulcer patients and in 2 (12%) controls (p less than 0.05). Secretin levels did not increase after duodenal acidification, the higher percentages of failure being observed in groups A and C (p less than 0.05). The pH of the duodenal aspirate was 4.9 +/- 2 and 7.7 +/- 1.4 in ulcer patients and controls, respectively (p less than 0.05), with the low levels being detected in groups A and C (4.7 +/- 2 and 5.3 +/- 2.1) compared to group B (7.3 +/- 1.7; p less than 0.05). The results show that responses of duodenal ulcer patients to duodenal acidification are heterogeneous, and that failure of gastric secretion inhibition and defective intraduodenal acid neutralization are related.     

Effect of pirenzepine on oesophageal, gastric, and enteric motor function in man

The effect of pirenzepine on oesophageal, gastric, and enteric motor function was evaluated in six healthy volunteers. Each subject was studied before and after taking pirenzepine, 100 mg/day, for 3 days. Half and complete gastric emptying times of clear liquid, assessed by epigastric impedance, were significantly delayed by the drug: 6.16 +/- 1.74 min and 13.8 +/- 4.64 min versus 16.65 +/- 3.03 min and 25.1 +/- 8.2 min, respectively (p less than 0.05). Enteric motility was assessed by manometry, and variables studied were the duration of the various phases of the migratory motility complex, the frequency of contractions in phase III, and the amplitude of contractions in phases II, III, and in the postprandial period. Only phase I was affected and was significantly prolonged by the drug: 16.08 +/- 5.94 min versus 31.65 +/- 12.88 min (p less than 0.01). Oesophageal motility was assessed by manometry. Variables studied were amplitude and duration of contractions in the body of the oesophagus, and lower oesophageal sphincter pressure. Results were not significantly changed by the drug. We conclude that pirenzepine, given at a dose used for treatment of peptic ulcer disease, significantly delays the gastric emptying of liquids, has minimal effect on enteric motility, and has no effect on oesophageal motility. The effect on gastric emptying may be therapeutically useful by reducing the acid load on the duodenum in duodenal ulcer disease.