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PubMed1994

Healing of NSAID-induced gastric ulcers with a synthetic prostaglandin analog (enprostil).

OBJECTIVE: Conventional ulcer therapy has not been proven effective in healing gastric ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) if the NSAIDs are continued. Our objective in this study was to determine whether a prostaglandin analog is an effective treatment for such NSAID-induced lesions. METHODS: To make this determination, we conducted a 9-wk double-blind trial comparing placebo with enprostil 35 micrograms twice daily and three times daily. Use of antacids was not allowed. Three centers entered 145 patients with chronic inflammatory arthritis and osteoarthritis, mean age 63 yr, who required continuous fixed-dose NSAID therapy within the range of therapeutic dosage. The minimum entrance criterion was the presence of either four gastric erosions or one gastric ulcer. Two pretreatment endoscopies within a 2-wk interval were performed to establish the presence of stable baseline gastric lesions. Endoscopy was repeated at wk 6 and 9 during treatment. All groups were similar with regard to age distribution, sex, weight, height, smoking usage, and alcohol consumption. RESULTS: The ulcer healing rates were 14%, 57%, and 68% at 6 wk and 19%, 68%, and 74% at 9 wk for the groups receiving placebo, enprostil twice daily, and enprostil three times daily, respectively (p < 0.01). Complete mucosal healing of all erosions and ulcers at 9 wk occurred in 59% of enprostil-treated patients and in 10% of placebo-treated patients. Additional gastric erosions and gastric ulcers developed in 16% of placebo patients and 4% of the enprostil patients. Eighteen percent of enprostil patients withdrew early from the study due to adverse experiences, such as diarrhea and abdominal pain. CONCLUSION: We concluded that during continued NSAID therapy 1) enprostil 35 micrograms (taken either twice daily or three times daily) heals NSAID-induced gastric ulcers and erosions and protects the mucosa from further NSAID-induced gastric injury; 2) gastric ulcers and erosions rarely heal spontaneously, and 3) enprostil results in a high incidence of diarrhea.

Aged↗
PubMed1986

Reactivity of enprostil stereoisomers in soft elastic gelatin capsules.

Enprostil (methyl 7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1-butenyl]- 5-oxocyclopentyl]-4,5-heptadienoate), a gastric acid secretion inhibitor and potent anti-ulcer drug, is formulated as a propylene carbonate solution which is filled into soft elastic gelatin capsules. The drug molecule features two unresolved asymmetric carbon atoms, and synthesis yields an equimolar mixture of four different optical isomers (two diastereomeric pairs of enantiomers). The objective of this study was to establish the degree to which enprostil does or does not degrade stereoselectively in the soft elastic gelatin capsule formulation. Accordingly, we developed an HPLC method capable of resolving enprostil diastereoisomers and applied the method to determining reaction rates of enprostil in soft elastic gelatin capsules maintained at 40 degrees C. The study included three soft elastic gelatin capsule lots: the first two contained an equimolar mixture of all four enprostil enantiomers; and the third contained an equimolar mixture of two individual diastereoisomers of known optical purity. Comparing enprostil degradation rates in the three capsule lots showed that reactivity ratios in all cases were (within the limits of experimental uncertainty) equal to unity. This observation conclusively excludes the possibility of significant enantioselectivity for enprostil degradation in the soft elastic gelatin capsule formulation. We also report kinetic equations for the general case of relating stereospecific reactivity ratios to drug product shelf life when drug concentrations are monitored with nonstereoselective analytical techniques.

Capsules↗
PubMed1994

Effect of synthetic prostaglandin E2 analog enprostil on omeprazole-induced hypergastrinemia and hyperpepsinogenemia.

This study was undertaken to determine whether the synthetic prostaglandin E2 analog enprostil is able to inhibit basal and postprandial hypergastrinemia induced by omeprazole. We also studied the effect of omeprazole, enprostil, and the combination of both drugs on serum pepsinogen A and C levels. Eight normal subjects received in random order five-day courses of 40 mg omeprazole once a day, 35 micrograms enprostil three times a day, the combination of both drugs, and placebo. Omeprazole induced significant increases in basal and postprandial serum gastrin and in pepsinogen A and C levels. These increments persisted on the day after stopping treatment. Coadministration of enprostil inhibited omeprazole-induced basal hypergastrinemia and postprandial integrated serum gastrin, but not basal serum pepsinogen A and C, while the inhibition on the day after the treatment courses only reached statistical significance for the postprandial integrated serum gastrin concentration. It is concluded that enprostil inhibits omeprazole-induced basal and postprandial hypergastrinemia, with a tendency to protracted inhibition after stopping the drugs, and that enprostil does not significantly influence omeprazole-induced increases in pepsinogen A and C level. Coadministration of enprostil may be helpful in preventing pronounced hypergastrinemia in the few patients who show large serum gastrin increases during treatment with omeprazole.

Adult↗
PubMed1997

Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole.

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10 micrograms/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Central and peripheral effects of prostaglandin E2 and enprostil on gastric acid secretion in the rat.

The intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) inhibits gastric secretion at doses that are inactive by i.v. administration in the rat. The present study was undertaken to examine the central and peripheral effects of enprostil, a potent synthetic PGE2 analogue, on gastric acid secretion as compared to those of PGE2. We used conscious rats equipped with a chronic gastric fistula and a cannula to allow injection into the third ventricle of the brain. Gastric acid output was measured under basal interdigestive conditions and during stimulation with submaximal doses of pentagastrin and histamine. Total inhibition of basal and stimulated gastric acid output was obtained after i.c.v. PGE2 and after i.c.v. or i.v. enprostil administration. After i.v. PGE2, the maximal observed inhibition was not greater than 50%. The ratio of ED50 values for i.v. administered to i.c.v. administered PGE2 was 64 or more, whereas the ratio of ED50 values for i.v. enprostil to i.c.v. enprostil was 9 to 13. Under all conditions studied, enprostil was more potent than PGE2 and this greater potency was more prominent after i.v. administration (ratio 250 to 2500) than after i.c.v. administration (ratio 10 to 400). The blockade of alpha 2-adrenoceptors by idazoxan did not suppress the inhibition of gastric secretion produced by i.c.v. PGE2 or enprostil. It is concluded that low doses of PGE2 inhibit gastric acid output mainly through a central mechanism, whereas low doses of enprostil potently inhibit gastric acid output through both a central and a peripheral mechanism. alpha 2-Adrenoceptors are not essential for the effect of i.c.v. prostanoids on gastric acid secretion.

Adrenergic alpha-Antagonists↗
PubMed1989

Enprostil reduces the increase of gastric corpus mucosal mass induced by the hydrogen-potassium-stimulated adenosine triphosphatase inhibitor BY 831-78 in the rat.

We studied whether enprostil, a synthetic prostaglandin E2 derivative, might inhibit gastrin release and the trophic effects on gastric oxyntic mucosa induced by prolonged treatment with an inhibitor of hydrogen-potassium-stimulated adenosine triphosphatase, the substituted benzimidazole BY 831-78. Rats were treated intragastrically with enprostil (1 or 15 micrograms/kg b.i.d.), BY 831-78 (15 mumol/kg once daily), the combination of enprostil and BY 831-78, ranitidine (300 mumol/kg b.i.d.), and placebo. Plasma gastrin and somatostatin levels and gastric acid secretion were measured during a 1-day treatment in animals fitted with chronic gastric fistulas and repeatedly during 9 wk of treatment in intact rats. Despite inhibiting acid secretion, enprostil did not increase plasma gastrin. When combined with BY 831-78, enprostil transiently reduced the BY 831-78-induced increase of integrated plasma gastrin (1375 +/- 206 vs. 2137 +/- 256 pmol/L.12 h, p less than 0.05) in fasted rats with fistulas, but failed to prevent the marked hypergastrinemia following 9 wk of treatment with BY 831-78 (717 +/- 80 vs. 731 +/- 56 pmol/L) in intact rats. However, enprostil reduced the BY 831-78-induced increase of oxyntic mucosal volume (458 +/- 31 vs. 567 +/- 33 mm3, p less than 0.01), whereas BY 831-78 prevented the enprostil-induced increase of antral mucosal volume (42 +/- 3 vs. 56 +/- 3 mm3, p less than 0.01). These results demonstrate that some of the trophic effects induced by a hydrogen-potassium-stimulated adenosine triphosphatase inhibitor are not exclusively governed by gastrin.

Adenosine Triphosphatases↗
PubMed1986

Stimulation of HCO3- secretion by the prostaglandin E2 analog enprostil: studies in human stomach and rat duodenum.

This study investigated the action of enprostil, a synthetic analog of PGE2, on gastric HCO3- secretion in humans and on duodenal HCO3- secretion in the anesthetized rat. A previously validated 2-component model was used to calculate gastric HCO3- and H+ secretion in 10 human subjects. Compared to placebo, a single 70 micrograms oral dose of enprostil increased basal gastric HCO3- secretion from 1810 +/- 340 to 3190 +/- 890 mumol/hr (P less than 0.05). In addition, enprostil reduced basal gastric H+ secretion from 5240 +/- 1140 to 1680 +/- 530 mumol/hr (P less than 0.02). Enprostil also increased HCO3- secretion and reduced H+ secretion during intravenous pentagastrin infusion. In the rat, duodenal HCO3- secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary secretions. Addition of enprostil (10 micrograms/ml) to the duodenal bathing solution increased duodenal HCO3- secretion from 6.3 +/- 1.3 to 15.1 +/- 2.0 mumol/cm X hr (P less than 0.01, n = 6). The stimulatory action of enprostil on duodenal HCO3- secretion at 10 micrograms/ml was comparable in magnitude and duration to that of 10 micrograms/ml natural PGE2. In summary, the PGE2 analog enprostil stimulated gastroduodenal HCO3- secretion, effects which may be beneficial in protection of the gastroduodenal mucosa against luminal acid.

Adult↗
PubMed1986

Stimulatory effect of enprostil, an anti-ulcer prostaglandin, on gastric mucus secretion.

Enprostil, a synthetic analogue of prostaglandin E2, is known to be a potent inhibitor of gastric acid secretion, and has marked anti-ulcer activity in rodents. Enprostil was administered in doses ranging from 15 to 250 micrograms/kg to rats prepared using the Shay procedure. Three hours later, the rats' stomachs were removed and processed either for the chemical determination of mucus, or for scanning electron microscopy. For the chemical determination, the secreted gastric juice was removed and the adherent gastric mucus was eluted with 2 M sodium chloride. The anthrone method was used to determine the mucus present. Enprostil was found to significantly increase gastric mucus at a dose of 60 micrograms/kg when measured by the anthrone test. Enprostil administered by the oral route was most effective in stimulating mucus secretion, suggesting a local or topical action of enprostil on mucus-secreting cells. Scanning electron microscopy of rat fundic mucosa after enprostil administration (50 to 100 micrograms/kg) revealed the presence of thin veil-like layers covering the epithelial surface, which was interpreted as an increase in mucus secretion. Higher magnifications (X 2,000) clearly showed the layers of mucus covering the surface epithelial cells. Enprostil's apparent increase of gastric mucus secretion may contribute to its anti-ulcer activity and may promote gastric healing.

Administration, Oral↗
PubMed1986

Protective effect of enprostil against aspirin-induced gastroduodenal mucosal injury in man. Comparison with cimetidine and sucralfate.

A single-blind endoscopic study was undertaken to test the relative efficacy of enprostil, a synthetic analogue of prostaglandin E2, cimetidine, and sucralfate in the prevention of aspirin-induced gastroduodenal mucosal injury. Fifty healthy, non-smoking male volunteers completed the study after having been randomly assigned to receive two weeks of therapy with one of the following regimens: enprostil 35 micrograms twice daily; enprostil 35 micrograms in the morning; cimetidine 200 mg three times daily and 400 mg at night; sucralfate 1 g four times daily; or placebo. In the second week, aspirin (900 mg three times daily) was also administered. Endoscopies were performed before and after the aspirin phase of the study, and lesions (mucosal erosions plus submucosal hemorrhages) were counted in the stomach and duodenal bulb. All treatments were superior to placebo (p less than 0.05). The mean number of lesions in the 70-micrograms enprostil group (8.5) was significantly less than in the 35-micrograms enprostil group, (11.1), the sucralfate group (12.4), or the placebo group (16.0); the benefit over cimetidine (10.1), however, was not statistically significant. The protective effect of enprostil was greatest in the antrum, the site of maximal mucosal injury. Gastrointestinal side effects were reported in all groups, though abdominal pain and dyspepsia were noted more frequently in those taking enprostil.

Adult↗
PubMed1986

Comparative clinical trial of enprostil and ranitidine in the treatment of gastric ulcer.

In a randomized, double-bind, parallel, multi-clinic study, the safety and efficacy of enprostil (35 micrograms twice daily) and ranitidine (150 mg twice daily) were compared in the treatment of active gastric ulcer in 93 outpatients (47 enprostil-treated patients and 46 ranitidine). The two treatment groups were well matched for demographic characteristics. The healing rates in the enprostil group were 22, 58, 80, and 86 percent at two, four, six, and eight weeks, respectively. The corresponding rates in the ranitidine group were 22, 66, 84, and 89 percent. None of these differences was statistically significant. The area of the ulcer at baseline and smoking status did not appear to influence healing rates. There were no significant differences between treatment groups in time to relief of ulcer symptoms, frequency of daytime or nighttime ulcer pain, or antacid use. Side effects attributable to enprostil treatment were diarrhea (10 percent versus 6 percent with ranitidine), gastrointestinal pain, and vomiting. These side effects, however, did not influence the patients' assessments of their overall response to enprostil and ranitidine therapy. Six enprostil-treated patients and one ranitidine-treated patient withdrew from the trial prematurely because of adverse experiences. Monitoring of clinical laboratory test results showed no significant changes in the two treatment groups. This study demonstrates that a prostaglandin E2 analogue, enprostil, in a dose of 35 micrograms twice daily, is similarly safe and effective as ranitidine in the treatment of active gastric ulcer.

Adolescent↗
PubMed1988

Suppression of postprandial glucose, insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) in man by oral administration of a prostaglandin analogue (enprostil).

Enprostil, a long-acting, orally active dehydroprostaglandin E2 with cytoprotective and gastric antisecretory properties, is a potent inhibitor of meal-stimulated gastrin release. Recent data have suggested suppression of additional other gastrointestinal peptide hormones following single doses of enprostil. The current investigation was conducted to further clarify the effects of enprostil administration on gastrointestinal hormones and glucose metabolism under physiologic conditions and to determine whether these effects were present following multiple doses of the agent. Enprostil 70 mcg/d and its placebo were each administered for 7 1/2 days to eight normal male subjects in a study of crossover design, each treatment period lasting 7 1/2 days and separated by a 7 day washout period. Subjects received a test meal on days 1 and 8 and an oral glucose challenge on day 3 of each treatment period following enprostil or its placebo. Following the test meal, there was a delay and suppression of the maximum measured serum glucose levels. Mean overall peak glucose concentrations were lower during the enprostil phase compared to placebo (112 vs. 121 mg/dd, P = 0.025) with a trend toward delay in the time to achievement of peak glucose concentrations. Mean overall peak levels for insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) were significantly suppressed by 36%, 16% and 60%, respectively by enprostil when compared to placebo. The overall integrated postprandial responses for insulin, C-peptide, and GIP were significantly reduced by 42%, 39% and 90%, respectively while that for glucose above baseline was reduced by 44% (P = 0.098). Similar effects were present following the oral glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Effect of enprostil on the gastroduodenal mucosa of healthy volunteers.

Enprostil is a synthetic dehydro-prostaglandin E2 with gastroduodenal ulcer-healing and mucosal-protective properties. One hundred and three healthy volunteers were randomized to receive capsules of enprostil 35 micrograms b.d. (the clinically recommended dose), enprostil 70 micrograms b.d., or placebo b.d. All underwent endoscopic assessment of the gastroduodenal mucosa, scored using a 0-4 scale, at baseline and on Days 3, 7, 14, 21 and 28 of dosing. Mean and median maximum scores demonstrated a dose response, and the mean maximum scores were statistically significantly higher for both enprostil groups on each endoscopy day when compared with placebo. The majority of enprostil-treated subjects had petechial haemorrhages. The proportion of volunteers with small white-based mucosal breaks (erosions) was significantly higher for the fundus in the enprostil 70-microgram group on Days 21 and 28 when compared with placebo, but there were no significant differences between treatment groups for any area on the other study days. The 70-microgram dose was associated with significantly more gastrointestinal adverse events than the 35-microgram dose, which was similar to placebo. There were no significant differences between groups for large white-based mucosal breaks (ulcers). We conclude that oral enprostil produced gastric mucosal petechial haemorrhages, primarily in the fundus of the stomach. Gastric mucosal petechial haemorrhages are probably without clinical significance because they are very common in the general population (10-15%) and do not progress to erosions and ulcers.

Double-Blind Method↗
PubMed1994

Effect of enprostil on serum gastrin and pepsinogen A and C levels in patients on long-term treatment with omeprazole.

BACKGROUND: Treatment of omeprazole induces profound inhibition of gastric acid secretion, resulting in hypergastrinaemia. In rats hypergastrinaemia induced by chronic administration of high doses of omeprazole resulted in ECL-cell hyperplasia and subsequent carcinoid formation. This finding may limit long-term therapy in man. The synthetic prostaglandin E2 analogue enprostil not only inhibits gastric acid secretion but also reduces serum gastrin in normal subjects and in peptic ulcer patients. The present study was undertaken to determine whether enprostil reduces serum gastrin in patients on long-term treatment with omeprazole. METHODS: Eight patients with reflux oesophagitis treated with 40 mg omeprazole once daily for at least 3 months received 35 micrograms enprostil t.d.s. during a 5-day treatment course. Basal and postprandial serum gastrin concentrations and pepsinogen A and C levels were measured on the day before, the first and the final day, and on the day after cessation of treatment. RESULTS: Enprostil significantly (P < 0.05) reduced basal serum gastrin from 65 +/- 15 pmol/L to 51 +/- 13 pmol/L on the first treatment day, and to 41 +/- 9 pmol/L on the final day. Enprostil also significantly (P < 0.05) reduced postprandial integrated serum gastrin from 6173 +/- 849 pmol.h/L to 4516 +/- 906 pmol.h/L and to 3532 +/- 706 pmol.h/L on the first and final treatment days, respectively. On the day after cessation of treatment basal (57 +/- 11 pmol/L) and postprandial integrated serum gastrin concentrations (5766 +/- 864 pmol.h/L) were not significantly different when compared to pretreatment values. Enprostil had no significant influence on serum pepsinogens A and C. CONCLUSION: Short-term co-administration of enprostil lowers the serum gastrin levels in patients on long-term treatment with omeprazole.

Aged↗
PubMed2000

Effect of intrarectal prostaglandin E2 analogue (enprostil) on trinitrobenzenesulphonic acid-induced colitis in rats.

Prostaglandins exert a protective effect on colonic mucosa in experimentally induced colitis. This study investigated the effect of enprostil, a prostaglandin E2 (PGE2) analogue, on trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats. Each rat received a rectal enema containing TNBS (30 mg), followed 24 h later by intrarectal once-daily enprostil (200 microg). Enprostil-treated and control rats were killed on day 3 (enprostil group, n = 5; control, n = 6) or day 10 (enprostil group, n = 5; control, n = 5) after TNBS treatment. The area of damaged mucosa of the colon was measured relative to the total colonic area. We also determined the macroscopic score of mucosal damage, and measured PGE2, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) concentration in portal vein blood samples. Enprostil significantly reduced both the area of damaged mucosa (including the ulcer area) and the macroscopic score after 3 days' treatment compared with control. Similarly, enprostil significantly reduced plasma concentration of PGE2, 6-keto-PGF1alpha and TXB2 during the acute phase at day 3 of treatment compared with control, but not at day 10. These results suggest that PGE2 enema may have therapeutic potential for treating patients with proctitis or left-sided colitis.

Animals↗
PubMed1990

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 70 micrograms) 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 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 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 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.

Administration, Oral↗
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 4th communication: effect on hepatic drug metabolizing enzyme system in rats.

Effects of multiple oral administration of enprostil ((+/-)-11 alpha,15 alpha-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorprosta- 4,5,13(t)-trienoic acid methyl ester, TA 84135) (20 micrograms/kg/d) and its solvent propylene carbonate (PC, 100 microliters/kg/d) on body weight gain, liver weight, hepatic drug metabolizing enzyme system and hexobarbital sleeping time were investigated in male rats during a 14-day period. Cytochrome P-450 content (as compared to the untreated control) and cytochrome b5 content (as compared to PC treated group) were slightly, but significantly, reduced in the group given a single oral dose of enprostil. However, these slight reductions were not augmented significantly by repeated administrations of enprostil. Slight but significant increase in microsomal protein content was observed in the group given 14 oral doses of enprostil and PC. Enprostil did not affect the other indicators used to evaluate the status of the hepatic drug metabolizing enzyme system. Additionally, single or multiple oral doses of enprostil or PC showed no effect on the hexobarbital-induced sleeping time. It therefore may be safely concluded that multiple oral administration, both of enprostil and of PC, has very little effect on drug metabolizing enzyme inducing or inhibiting activity in rats.

Animals↗
PubMed1989

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.

Adult↗
PubMed1990

Effect of two-week treatment with enprostil (35 micrograms 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.

Adult↗