Gastric antisecretory activity of 15(R)-15-methylprostaglandin E2, arbaprostil, in dogs.

The gastric antisecretory activity of 15(R)-15-methylprostaglandin E2 (arbaprostil) was compared with that of natural prostaglandin (PG) E2 in Pavlov pouch dogs. Arbaprostil significantly inhibited pentagastrin- and food-stimulated gastric secretion when it was administered directly into the pouch at a dose of 10-30 micrograms/pouch and 30-300 micrograms/pouch, respectively. Natural PGE2, however, was inactive up to 1000 micrograms/pouch. The data indicate that arbaprostil is a potent, long-acting orally active antisecretory drug that may be useful for the treatment of peptic ulcer disease.

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.

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.

Pharmacokinetic interactions between arbaprostil and aspirin in humans.

Arbaprostil is an orally active prostaglandin E2 analogue. It has been developed as a drug to treat ulcers induced by non-steroidal anti-inflammatory drugs. In this study, pharmacokinetic interactions between arbaprostil and aspirin were examined in humans after chronic doses of both drugs. Subjects received either arbaprostil (50 micrograms), aspirin (975 mg) or arbaprostil (50 micrograms) and aspirin (975 mg) four times a day for 6 days and one dose on 7th day. Blood and urine samples were collected after the last dose for 6 h. Pharmacokinetic parameters of arbaprostil, aspirin, and salicylate were determined. Coadministration of arbaprostil significantly lowered the area under curve (5.09 +/- 0.32 micrograms hml-1 vs 5.78 +/- 0.29 micrograms hml-1, mean +/- SE, p less than 0.05) and time (0.45 +/- 0.07 h vs 0.70 +/- 0.12 h, p less than 0.05) to reach maximal plasma concentration of aspirin (acetylsalicylate). The pharmacokinetics of salicylate were not changed by arbaprostil, nor were the pharmacokinetics of arbaprostil affected by aspirin. Coadministration of these two drugs did not appear to potentiate the side-effects of either drug. The results suggest that arbaprostil and aspirin may be administered together without clinically significant changes in pharmacokinetics or adverse side-effects.

Pregnancy termination: techniques, risks, and complications and their management.

PIP: This article outlines the current modalities of pregnancy termination, as well as their risks and complications, in 3 phases of pregnancy: 1) up to 49 days past the last menstrual period, 2) 8-15 weeks, and 3) 16-24 weeks. Before 8 weeks of pregnancy, suction dilatation and curettage (D and C) is the preferred method. However, a medical approach, possibly self-administered, is viewed as more satisfactory and requires only an improvement in side effects. From 8-15 weeks' gestation, suction D and C and dilatation and evacuation (D and E) are the methods of choice. The use of laminaria tents improves both the facility and safety of these procedures in nulliparous patients and perhaps in multiparous patients. Priming of the cervix with prostaglandin could further decrease the difficulty and risks of these procedures. The use of a hydrogel compound is especially worthy of consideration. There is controversy about the preferred method between 16-20 weeks' gestation. D and E appears to have fewer complications and to be more cost-effective than hypertonic saline injection. Urea-prostaglandin has fewer and less severe complications than saline injection, and seems to be more cost-effective than saline injection in terms of duration of hospitalization. The high frequency of failure and side effects, combined with the possibility of expulsion of a live fetus, make prostaglandin-only injection less desirable. After 20 weeks' gestation, urea-prostaglandin injection is probably the safer method. Given the rapid increase in complications with passing weeks, any delay in providing late abortion services should be avoided. 2nd trimester pregnancy terminations, especially those after 18 weeks' gestation, are associated with increased mortality and morbidity and should be performed at specialized centers where providers are better equipped to manage complications.^ieng

Effect of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on the healing of duodenal ulcer: a double-blind multicenter study.

A multicenter study was conducted on 173 patients with active, endoscopically proven duodenal ulcers (158 men, 15 women). They were randomly assigned, in a double-blind manner, to two groups: those receiving placebo capsules (91 patients) and those receiving capsules containing 100 microgram of 15(R)-15-methyl prostaglandin E2 (arbaprostil) (82 patients). Each drug was ingested four times a day (1 h before meals and at bedtime) for 28 days. Endoscopy was performed on days 0, 14, and 28 after the trial began. At each examination, the ulcer size was measured and whether the ulcer had healed was recorded. Arbaprostil increased the incidence of ulcer healing to approximately the same degree as reported in most extensive studies with cimetidine. At 14 days, three times as many patients were totally healed in the arbaprostil-treated as in the placebo-treated group (37% vs. 12%, p less than 0.001). At 28 days, 67% of patients receiving arbaprostil were healed compared with 39% in the group receiving placebo (p less than 0.001). Similarly, the ulcer size, measured endoscopically, was much smaller after arbaprostil administration than in the group receiving placebo after both 14 and 28 days (p less than 0.001). Side effects attributable to treatment consisted primarily of loose stools and diarrhea (34%). Smoking retarded healing in the placebo-treated group (p less than 0.05), but did not significantly retard healing in patients treated with arbaprostil. We conclude that arbaprostil markedly accelerates the healing rate of active duodenal ulcers. This effect may be due to inhibition of acid secretion as well as gastric cytoprotection.