Twenty-four-hour intragastric measurements in twenty healthy subjects: effect of enisoprost, a novel and potent antisecretory and antipeptic synthetic E1 prostaglandin.

Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.

Focus on misoprostol: review of worldwide safety data.

Gastrointestinal symptoms have been the most frequently reported adverse experiences in the misoprostol (Cytotec) studies of both patients with peptic ulcer disease, and healthy subjects. There have been relatively few cardiovascular, genito-urinary, or other adverse effects. This is similar to the results of animal studies in which misoprostol had little, if any, effects on cardiovascular, central nervous, and endocrine systems. The predominant activity of misoprostol in the gastrointestinal tract, essential to its ulcer-healing activity, may also account in part for the association of misoprostol with gastrointestinal adverse experiences. Abnormal bowel movements were the most common complaint (9-13%) of patients in pivotal controlled studies. In patients taking misoprostol 200 micrograms four times daily, 7.1% had diarrhea, with less than 1% stopping therapy because of diarrhea. Abdominal pain in these patients was reported in an incidence of 12.8%, was mild, and only rarely resulted in stopping therapy. Other adverse reactions reported in these patients were nausea, headache, and dizziness. In pregnant women, undergoing a legal termination of pregnancy, it has been shown that misoprostol has a greater incidence of uterine bleeding, and partial or complete expulsion of uterine contents, than placebo. Misoprostol (Cytotec) has received government approval for marketing in 12 countries, since the first gave its approval in June, 1984. It has been launched in 6 of those markets to date, with an estimated 100,000 patients having taken the drug. No serious adverse experiences attributed to misoprostol have been reported, but mild adverse experiences have occurred. Those most frequently reported were gastrointestinal in nature, and included diarrhea, abdominal pain, and nausea.(ABSTRACT TRUNCATED AT 250 WORDS)

A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction.

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.