Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

BACKGROUND/AIMS: Human milk fortification has been advocated to enhance premature infants' growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. METHODS: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. RESULTS: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 +/- 2.1 vs. 144.4 +/- 2.5 ml/kg/day, mean +/- SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 +/- 1.3 and 20.4 +/- 1.2 g/day, p < 0.05; head circumference 1.0 +/- 0.1 and 0.8 +/- 0.1 cm/week; length 0.9 +/- 0.1 and 0.8 +/- 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. CONCLUSIONS: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants.

OBJECTIVE: To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN: Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING: Ambulatory-care facilities of the participating centers. SUBJECTS: 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION: Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES: Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED: Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS: One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS: This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.

A metabolic balance study in term infants fed lactose-containing or lactose-free formula.

Lactose-free (L-) formulas are recommended for infants with conditions affecting lactose digestion. Cows' milk protein-based formulas containing other carbohydrate sources are most often used for such infants. This study compared fat absorption and absorption and retention of nitrogen, calcium, phosphorus, and magnesium in term infants fed either a L- or standard lactose-containing (L+) bovine milk protein-based formula. Data from three single-centre, double-blind, randomized, parallel-group metabolic balance studies were combined. After a 4-7-d equilibration period on either L- or L+ formula, a 72-h balance study was performed. Twenty infants received L- and 21 received L+ formula. Besides the L- group having a higher percentage of males (65%) and the L+ group a higher percentage of females (52.4%), other baseline measurements were similar. The majority of nutrient balance data was similar between the two groups. Exceptions were relative nitrogen absorption, calcium intake and calcium retention, magnesium retention, and faecal phosphorus excretion, all of which were significantly higher in the L- group. Vitamin D supplementation did not significantly affect either calcium or phosphorus data. This new L- formula provided similar nutrients and is a suitable alternative to a L+ formula in term infants requiring L- feedings.

Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids.

This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula (Preemie SMA) devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32-1.1% AA and 0.24-0.75% DHA in the fat component of the formula. An analogous group of infants fed on their mothers' breast milk and a breast milk fortifier was also studied. Individual lipoprotein fractions were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. The fatty acid content of individual lipid components, isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid. The high density lipoproteins (HDL) and low density lipoproteins (LDL) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions (total of 0.49% and 0.35%, respectively). Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction. A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the level of AA found in the HDL and LDL phospholipid fraction. From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49% AA and 0.35% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined.

Upper respiratory tract complications of gastroesophageal reflux in adult and pediatric-age patients.

Upper airway complications of gastroesophageal reflux occur much less frequently than those abroad to the upper esophageal sphincter; however, laryngitis, laryngeal and/or tracheal stenosis, globus syndrome, oropharyngeal dysphagia, otitis media, sinusitis, and rhinitis can all be associated with significant morbidity and occasional mortality in both adult and pediatric patients. Sudden infant death and apparent life-threatening events, both found only in pediatric patients, are even less frequently associated with gastroesophageal reflux. Today, excellent diagnostic methods are available, such as proximal 24-hour pH probe evaluations or scintigraphy, making proper diagnosis much easier than previously. Although today's medical and surgical methods do not affect the underlying pathophysiology, they are frequently very effective in controlling signs and symptoms, allowing the patients to return to resume their normal life-styles and livelihoods.

Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids.

The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), have not been clearly defined. The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula (Preemie SMA) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1% AA and 0.24 to 0.76% DHA. An analogous group of infants fed their mothers' breast milk and a breast milk fortifier (when indicated) was also studied. Erythrocyte membrane phospholipids were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine, and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids. From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32-1.1% AA and 0.24-0.76% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined.

Gastric acid suppression is greater during intravenous ranitidine infusion versus bolus injections of famotidine.

It has been proposed that famotidine may be effective in maintaining intragastric pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress-related mucosal haemorrhage. The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion. Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated in two 24-h treatment periods; each test was in random order separated by 7-10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12-h intervals in suppressing gastric acid secretion and maintaining an intragastric pH > or = 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.

Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome.

Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome is increasingly required; however, existing methods of determining the required dose are cumbersome and not applicable in all centers. A previous study suggested that the required parenteral dose of histamine H2-receptor antagonists correlated with the previous oral dose. In the present study, in 31 patients with Zollinger-Ellison syndrome we evaluated the hypothesis that an effective parenteral histamine H2-receptor antagonist dose could be predicted from the previous oral dose. Twenty-three patients were taking oral ranitidine (mean 1.3 g/day), six patients famotidine (152 mg/day), and two patients cimetidine (1.8 g/day). Each patient was treated with a continuous intravenous infusion of the equivalent dose of ranitidine (mean dose 1 mg/kg/hr with 35% requiring 0.5 mg/kg/hr, 49% 1 mg/kg/hr, 3% 1.5 mg/kg/hr, 10% 2 mg/kg/hr, and 3% 2.5 mg/kg/hr. This dose of ranitidine acutely controlled acid secretion (< 10 meq/hr) in all patients. To evaluate long-term efficacy and safety, 20 patients were maintained on this dose through the peri- and postoperative periods. Mean duration was 7.1 days with 25% treated 3-5 days, 40% 6-8 days, 30% 8-10 days, and 5% > 10 days. The predicted dose continued to control acid secretion in 95% of patients with one patient requiring one dose adjustment. No biochemical, clinical, or hematological toxicity was seen, although ranitidine was stopped in one patient because of skin rash. These results demonstrate that the parenteral dose of ranitidine required to control acid secretion in patients with Zollinger-Ellison syndrome can be predicted from the oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Ranitidine 300 mg at bedtime is effective for gastric ulcers: a 12-wk, multicenter, randomized, double-blind, placebo-controlled comparison. The Ranitidine 300 mg HS Gastric Ulcer Study Group.

Ranitidine 150 mg twice daily is effective for the treatment of gastric ulcers. We proposed that ranitidine 300 mg once daily would also be effective. In a randomized, double-blind, placebo-controlled, multicenter, parallel-group study, adults with an endoscopically verified acute gastric ulcer > or = 5 mm were treated with either ranitidine 300 mg (n = 183) or placebo (n = 178) at bedtime for up to 12 wk. Gastric ulcer healing, determined by endoscopy, was achieved in 65% and 89% of ranitidine-treated patients by 6 and 12 wk, compared with 45% and 72% of placebo-treated patients by 6 wk and 12 wk (p < 0.001). Throughout the 12-wk study, ranitidine 300 mg was significantly more effective than placebo in relieving pain (p < 0.05), with ranitidine-treated patients also using fewer antacid tablets. Ranitidine 300 mg had a safety profile similar to that of placebo. We conclude that ranitidine 300 mg at bedtime is safe and effective for healing acute gastric ulcers.

Ranitidine is effective therapy for erosive esophagitis.

Two ranitidine dosages were compared for the treatment of erosive esophagitis in a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Adults with endoscopically verified erosive esophagitis were treated with either ranitidine 150 mg four times daily (n = 106), ranitidine 300 mg four times daily (n = 106), or placebo (n = 116) for up to 12 wk. Patients were also encouraged to adhere to lifestyle modifications (e.g., to elevate the head of bed, etc). Erosive esophagitis healing, determined by endoscopy, was achieved in 69% and 62% of ranitidine-treated patients by 8 wk and in 79% and 74% by 12 wk (150 mg and 300 mg, respectively) compared with 28% of placebo-treated patients by 8 wk and 40% by 12 wk (p < 0.001 ranitidine vs. placebo). Onset of heartburn relief occurred within 24 h of initiating either ranitidine dosage, and relief was maintained throughout the 12-wk study. Both ranitidine dosages displayed safety profiles similar to that of placebo. We conclude that ranitidine 150 mg or 300 mg administered four times daily is effective for healing erosive esophagitis and relieving its symptoms.

A 4-week, multicenter, duodenal ulcer healing trial comparing four escalating doses of ranitidine.

In a randomized double-blind 4-wk trial, ranitidine doses of 300 mg at bedtime (hs), twice daily (bid), three times daily (tid), and four times daily (qid) were compared in 629 patients with endoscopically confirmed duodenal ulcer(s). Endoscopies were performed at baseline and after 4 wk of therapy. Per protocol analysis revealed wk 4 healing rates that were significantly increased (p < or = 0.001) for the bid, tid, and qid groups, compared with the hs group. All treatments provided early symptomatic (ulcer pain) relief. No significant differences in adverse events or laboratory abnormalities were observed between groups. Ranitidine 300 mg bid provides an alternative therapeutic approach for patient populations at risk for ulcer complications. These patients include those with the following: a past history of an upper gastrointestinal hemorrhage, perforation, obstruction, penetration, or giant (> 2.0 cm) duodenal ulcer. The elderly and those with chronic unresponsive ulcerations may also be included in this population.

The safety of ranitidine in elderly versus non-elderly patients.

The authors conducted a retrospective review of 21 United States trials of ranitidine in acid peptic diseases and compared the adverse events in elderly (> or = 65 years) and nonelderly (< 65 years) patients. Ranitidine dosages ranged from 150 mg/day to 300 mg twice daily for treatment periods of 4 to 52 weeks. Of the 4041 patients included in this review, 402 elderly and 2188 nonelderly patients received ranitidine and 245 elderly and 1206 nonelderly patients received placebo; 29%, 29%, 32%, and 26% of these patients, respectively, reported some type of adverse event. When only drug-related adverse events (as judged by the investigators under blinded conditions) were evaluated, these percentages dropped to 2%, 2%, and 1% and 2%, respectively. Gastrointestinal adverse events (e.g., nausea and diarrhea) and central nervous system adverse events (e.g., headache and dizziness) were the most common (0.7% and 0.8%, respectively), with comparable incidence rates in the elderly and nonelderly patients. The authors conclude that ranitidine is as safe in elderly patients as it is in nonelderly patients. No difference in the incidence of adverse events was found between older and younger patients who received ranitidine or placebo.

Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy.

The results of four similarly designed, randomized, double-blind, placebo-controlled studies conducted to evaluate ranitidine as prophylaxis for NSAID-associated damage are reviewed. A total of 673 patients receiving therapeutic dosages of NSAIDs for arthritic or musculoskeletal conditions also received either ranitidine 150 mg twice daily (n = 343) or placebo (n = 330) for four weeks (two studies) or eight weeks (two studies). Endoscopic grading of mucosal lesions was based on a modified Lanza scoring system. All patients had normal baseline endoscopies. After four weeks of treatment a significant protective effect against duodenal mucosal lesions including duodenal ulcers (three studies) and gastric mucosal lesions including gastric ulcers (one study) was observed in patients who received ranitidine compared with those who received placebo. A meta-analysis of the four studies confirmed that significantly fewer patients receiving ranitidine than placebo developed duodenal ulcers (1% vs. 6%, P = 0.01). Endoscopic data at eight weeks from the two longer-term studies showed that duodenal ulcers occurred in ranitidine- and placebo-treated patients at a rate of 1% (2/137) vs. 8% (10/126) (P = 0.02), respectively, in one trial, and 0% (0/57) vs. 8% (4/49) (P = 0.02), respectively, in the other trial. No protective effect in the stomach was evident at eight weeks. We conclude that ranitidine is effective in preventing NSAID-associated duodenal ulcers and may be appropriate prophylaxis for certain high-risk patients.

Evaluation of two monkey species (Macaca mulatta and Macaca fascicularis) as possible models for human Helicobacter pylori disease.

Endoscopic, histologic, and microbiologic evaluations of 21 cynomolgus and 34 rhesus monkeys for naturally occurring Helicobacter pylori infection were done. H. pylori was never isolated from any cynomolgus monkey, but was found in 12 rhesus monkeys. A general correlation existed between a positive culture and a gastric inflammatory response. Inoculation challenges were then undertaken. Four cynomolgus and five rhesus monkeys received two different H. pylori strains isolated from humans. Five rhesus monkeys received an isolate obtained from rhesus monkeys. Evaluation of the cynomolgus monkeys 7 and 14 days later revealed no H. pylori. Endoscopies of the rhesus monkeys were done 7, 14, 21, 28, and 56 days later. One rhesus monkey, which received the isolate from humans, became H. pylori positive at day 21 and remained positive through day 56. Restriction enzyme analysis of genomic DNA at day 56 revealed that the isolate was not identical to the challenge strain isolated from humans. All five rhesus monkeys that received the strain isolated from rhesus monkeys became H. pylori positive by day 14 and remained positive through day 56 Antral inflammation developed in all monkeys. Restriction enzyme analysis of genomic DNA on day 56 confirmed that four of five isolates were identical to the challenge strain isolated from rhesus monkeys. DNA hybridization documented homology between the challenge strains isolated from humans and rhesus monkeys plus those isolated at day 56. In this study, we showed that the rhesus monkey, if given a strain of H. pylori isolated from rhesus monkeys, develops a gastric infection with accompanying histological changes, making this model suitable for further development.

A report of three multiclinic trials evaluating arbaprostil in arthritic patients with ASA/NSAID gastric mucosal damage. The Upjohn Company Arbaprostil ASA/NSAID Gastric Mucosal Damage Treatment Study Groups.

Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.

Gastric emptying and the pharmacokinetics of the cephalosporin antibiotic, cefpodoxime proxetil.

The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug.

An evaluation of arbaprostil at multiple doses for the treatment of acute duodenal ulcer: a randomized double-blind placebo-controlled international trial.

Six hundred and thirty patients were enrolled in a randomized double-blind placebo-controlled trial evaluating two arbaprostil dosages (25 micrograms and 50 micrograms) qid for 4 wk for the treatment of acute duodenal ulcers. The healing rates in the placebo, 25-micrograms, and 50-micrograms treatment groups were 39%, 51%, and 60%, respectively. Smoking was found to adversely affect the healing rates in all the treatment groups. Pain severity was less with either arbaprostil treatment. The only side effect found was diarrhea: 10%, 14%, and 32% in the placebo, 25-micrograms, and 50-micrograms treatment groups, respectively. Severe diarrhea occurred in 1% of those patients who received the 50-micrograms dosage regimen, but in none of the other two groups. Arbaprostil at these two dosage levels, when given for 4 wk, appears to be a safe and efficacious agent for the treatment of acute duodenal ulcers.

The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil.

The effects of alteration of gastric pH and food on the pharmacokinetics of 200 mg doses of cefpodoxime proxetil tablets were studied in two separate randomized, open label, crossover studies in healthy subjects. In the pH study (n = 17 subjects), there was a lead-in period done under fasting conditions, followed by randomization to a four-way crossover of pentagastrin (6 micrograms/kg, subcutaneously), ranitidine (150 mg orally, 10 and 2 hours before dosing with the antibiotic), sodium bicarbonate (12.6 gm), or aluminum hydroxide (120 cc). Gastric pH was determined by nasogastric aspirates before and 10 minutes after the intervention, just before the antibiotic was given. Peak plasma concentrations (Cmax) and area under plasma concentration-time curve (AUC) were highest in fasting and pentagastrin periods and were 35% to 50% lower for all of the other periods (p less than 0.0001). Gastric pH and Cmax and AUC were inversely related (r = 0.66 and r = 0.62; p less than 0.0001 for both). In the food study (n = 16 subjects), there were two lead-in periods, one done while subjects were fasting and one while they were normal diet, followed by randomization to a four-way crossover of either high or low protein diets, or high or low fat diets. There were six meals in each diet. Dosing with the antibiotic was done at the midpoint of the fourth meal. Cmax and AUC were 22% to 34% higher for all diets than for the fasting period (p less than 0.0001), whereas the time to Cmax was unchanged. These studies demonstrated that absorption of cefpodoxime proxetil is best at low gastric pH or in the presence of food, which suggests that the role of gastrointestinal function on the pharmacokinetic profile is complex.

Arbaprostil's [15(R)-15-methyl PGE2] effects on intrauterine pressure in the nonpregnant and pregnant human female--a report of four clinical trials.

Four clinical trials evaluating arbaprostil's effects on the human uterus are reported. The initial two trials measured intrauterine pressures in nonpregnant and pregnant human females following arbaprostil doses of 10, 25, and/or 50 mcg. No statistical differences were found at any dosage level in either study for average uterine resting pressures, average peak pressures, the number of contractions or Montevideo units. Subsequently, two trials determined the abortifacient potential of arbaprostil in pregnant women during the first trimester. The first utilized total daily doses of 400 and 800 mcgs. while the second used total daily doses of 1200 and 1600 mcgs. Vaginal spotting was noted in one woman receiving 400 mcgs, three receiving 1200 mcgs. and in two receiving 1600 mcgs. One episode of moderate bleeding was seen in the latter study. Based on these studies, arbaprostil exhibits little potential for inducing abortifacient activity at these dosages in these patient populations.

Arbaprostil [15(R)-15-methyl prostaglandin E2] in a single nighttime dose of either 50 or 100 micrograms in acute duodenal ulcer.

To determine the efficacy of single nighttime doses of arbaprostil [15(R)-15-methyl prostaglandin E2], 50 or 100 micrograms for 4 wk, a double-blind randomized placebo-controlled multiclinic trial was undertaken. Success was defined as complete healing of the ulcer documented by endoscopy. Fifty-one of 64 patients enrolled were considered evaluable. Ulcer healing was documented in 64.3%, 85.7%, and 31.2% of the 100-micrograms arbaprostil, 50-micrograms arbaprostil, and placebo treatment groups (p value vs. placebo = 0.003 and 0.002, respectively). No difference in side effects or changes in laboratory parameters were found between the treatment groups except that diarrhea, usually mild, was found more often in the 100-micrograms arbaprostil group (60.0%) than in the 50-micrograms arbaprostil (31.8%) or placebo groups (23.5%) (p value 100 micrograms arbaprostil vs. placebo = 0.02). A single nighttime administration of arbaprostil seems to be a safe and efficacious agent for the treatment of acute duodenal ulcer.