[Antisecretory effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) on perfusing rats in vivo].

The antisecretion effect of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) was studied in perfusing rats in vivo. The results showed that PG6E at the dose 0.1 mg.kg-1 decreased markedly the acid secretion and antagonized the gastric acid secretion induced by histamine, pilocarpin and pentagastrin in rats. This action of PG6E appeared to be similar to that of cimetidine (40 mg.kg-1).

[Protection of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E) on experimental ulcers in rats].

The effects of dl-(15R)-15 methyl-PGE2 methyl ester (PG6E), in experimental ulcers induced by absolute alcohol, HCl, indomethacin, pyloric ligation and chronic acetic acid in rats were studied. PG6E at doses 10-80 micrograms.kg-1 was shown to have significant protective effect. PG6E (30-60 micrograms.kg-1) was also found to reduce markedly the acid secretion, pepsin activity, DNA content of the juice collected from pylorus ligated stomach of rats and increase markedly the content of gastric mucosa hexosamine in mice given PG6E (30-60 micrograms.kg-1 po for 3 d). At doses of 40-80 micrograms.kg-1, PG6E was able to have no significant effect on gastric emptying time in rats and gastrointestinal tract movement in mice. It appears that PG6E was shown to inhibit the aggressive factors and increase the protective factors of gastric mucosa. This may hopefully become a new antiulcer agent.

Comparative studies with 15(R)-15-methylprostaglandin E2 (arbaprostil) in rat femoral arterial preparations in vivo and in vitro.

1. The vasodilator responses to 15(R)-15-methylprostaglandin E2 (arbaprostil), prostaglandin (PG) E2 and acetylcholine (ACh) administered into the femoral artery intra-arterial (i.a.) of anesthetized rats were attenuated by i.a. infusion of methylene blue, while that to nicardipine remained unaffected in the same dose-range of methylene blue. 2. The vasocontractor responses to arbaprostil and PGE2 in isolated femoral arterial strips were significantly potentiated by removal of the endothelium and the presence of NG-monomethyl L-arginine, while that to U-46619 remained unaffected under the same condition. 3. The present result indicates that the endothelium-dependent mechanism may play an important role in the vascular response to arbaprostil, like PGE2 and ACh.

Protective effects of arbaprostil against indomethacin-induced gastric lesions in rats: significance of maintained gastric blood flow.

The purpose of the present study was to investigate the relationship between the effects of 15(R)-15-methylprostaglandin E2 (arbaprostil) on gastric blood flow (GBF) and its protective effects on gastric lesions in rats. The GBF of anesthetized rats was measured by two different methods: Total blood flow into the stomach (total GBF) was determined by means of an ultrasonic pulsed Doppler flow meter; and gastric mucosal blood flow (mucosal GBF) was measured by nonradioactive microspheres. Systemic blood pressure (SBP), heart rate (HR) and gastric vascular resistance (GVR) were recorded simultaneously. Arbaprostil (10-100 micrograms/kg) given i.v. did not affect resting total or mucosal GBF even though it decreased SBP and GVR. Significant improvement of the total and mucosal GBF decreased by indomethacin pretreatment (10 mg/kg, i.v.) was observed by administration of arbaprostil (10-100 micrograms/kg, i.v.) in a dose-dependent manner. Furthermore, i.v.-administration of this agent, in the same dose-range, prevented the formation of gastric lesions induced by indomethacin. The present result suggests that mitigation for the ischemic state of the gastric mucosa may be one of the important mechanisms for the prophylactic and curative effect of arbaprostil on gastric lesions induced by indomethacin.

Trophic doses of E2 prostaglandins do not influence the exocrine and endocrine pancreas in the presence of high levels of plasma somatostatin.

The aim of the present investigation was to study the effect of a long-term and a short-term treatment regimen with 15-R-15-methyl prostaglandin E2 and natural prostaglandin E2 (PGE2) on the endocrine cell populations of the rat pancreas. Graded oral doses of the analogue (5 and 50 micrograms/kg) and PGE2 (5000 micrograms/kg) were given twice daily for 4 weeks. The pancreas was carefully excised and weighed. Sections from randomly taken pancreatic biopsy specimens were processed for immunohistochemistry or hematoxylin and eosin staining before quantitative estimations were made, using stereologic methods. The total pancreatic volumes of insulin-, glucagon-, polypeptide P-, somatostatin-, and chromogranin A-immunoreactive cells were not affected by E2 prostaglandins. Neither the total volume of the islets of Langerhans nor that of the pancreatic cell nuclei was affected. The size of pancreatic cell nuclei was the same in the groups. The plasma levels of the antitrophic peptide somatostatin were significantly increased in rats treated with doses of both the analogue and PGE2 (p less than 0.05). In an additional short-term study rats were given oral placebo or 5000 micrograms/kg PGE2 twice daily for 5 days. The total endocrine pancreatic volume was not affected by PGE2. As in the long-term study, natural PGE2 did not affect the total pancreas volume or the total volume of pancreatic cell nuclei. These findings indicate that E2 prostaglandins produce no changes in the exocrine or endocrine pancreas in a dose range known to induce hyperplasia in the gastrointestinal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

E2 prostaglandins modulate cell proliferation in the small intestinal epithelium of the rat.

Groups of Sprague-Dawley rats were administered 1 mg/kg indomethacin subcutaneously, indomethacin subcutaneously plus 200 micrograms/kg oral 15-R-15 methyl-prostaglandin E2 (MePGE2) or oral MePGE2 twice daily for 10 days. The animals were treated with antibiotics to prevent mortality. Two control groups were used: control 1 was given placebo and control 2 was treated with antibiotics. All rats were killed 4 h after injection of a metaphase blocker, and the proliferative activity of the distal small intestine was examined in histological sections by means of the cumulative mitotic index (MI). A reduction in the number of villous cells was observed in the rats given antibiotics (p < 0.05 vs. control 1). The small intestinal villi of the rats treated with indomethacin had fewer cells than those of both control groups (p < 0.05) whereas the crypts contained more cells (p < 0.05) and had a higher MI than those of the controls (p < 0.05 vs. controls 1 and 2). These changes were reverted by the prostaglandin analogue. The number of cells of the small intestinal crypts and the cumulative MI in the rats who received indomethacin and the prostaglandin analogue were similar to controls, and they were significantly lower than the values observed in the animals treated with indomethacin (p < 0.05). The animals treated with the prostaglandin analogue and placebo developed a marked hyperplasia of the small intestinal villi (p < 0.05 vs. both control groups), but the atrophy of the villi induced by indomethacin was not prevented by simultaneous administration of the analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-promoted epimerization of arbaprostil, 15(R)-15-methylprostaglandin E2, elicits gastric antisecretory activities in rats.

Gastric acid antisecretory activities of 15(R)-15-methylprostaglandin E2 (arbaprostil) preincubated or not preincubated with 0.9% physiological saline, the pH of which was precisely adjusted to less than 4.30, were examined in pylorus-ligated rats, and compared with those of 15(S)-15-methylprostaglandin E2 (15(S), epimer of arbaprostil). 15(S), unlike arbaprostil without preincubation, when s.c.-administered to rats significantly inhibited gastric acid secretion in a dose-dependent manner (30-300 micrograms/kg). However, arbaprostil preincubated at 37 degrees C for 30 min with 0.9% saline, at pHs of 4.30, 2.75 and 1.20, respectively, showed the following order of pH-dependent antisecretory activities: 1.20 greater than 2.75 greater than 4.30. An increase in 15(S) formation from arbaprostil in a pH-dependent manner was also observed by radioisotopic experiments under the same incubation conditions using [3H]-labeled arbaprostil. The present result suggests that the gastric antisecretory effect of arbaprostil can be mainly explained in terms of the formation of 15(S) after oral administration.

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.

Prostaglandin E2-induced hyperplasia of the rat antral epithelium is followed by a secondary inhibition of the mitotic activity.

The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E2 prostaglandins during a prolonged period of time. Natural prostaglandin E2 (dose range: 0.2-5.0 mg.k-1) and 15 (R) 15 methyl prostaglandin E2 (dose range: 0.03-2.0 mg.kg-1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E2 and the synthetic analogue (p less than 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E2 did not affect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose who had a significantly lower mitotic index than controls (p less than 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E2 prostaglandins (p less than 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E2 might influence such regulatory mechanisms.

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.

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.

Effects of the synthesized prostaglandin E2-analogue arbaprostil on gastric mucosal lesions in rats.

The effects of arbaprostil (CU-83), a newly synthesized prostaglandin (PG) E2 analogue, on gastric lesions were investigated. Experiment 1: The animals were divided into 3 groups: 1. the control group: untreated, 2. 50% ethanol group: rats were given 1 ml of 50% ethanol intragastrically, and 3. arbaprostil + 50% ethanol group: arbaprostil (10 micrograms/kg) was administered p.o. 30 min before 50% ethanol administration. 1 h after ethanol administration, stomachs were isolated, and gastric mucosal lesions were observed. Experiment 2: Rats were divided into 4 groups; 1. the control group; untreated, 2. 6 h stress group; animals were placed in a stress cage and immersed into a water bath (23 degrees C) for 6 h, 3. arbaprostil (10 micrograms/kg) + 6 h stress group, and 4. arbaprostil (100 micrograms/kg) + 6 h stress group; arbaprostil 10 micrograms/kg or 100 micrograms/kg was administered 30 min before 6 h of water immersion stress, respectively. In each experiment, stomachs were isolated and gastric mucosal lesions were observed. Immediately after the observation of lesions, the fundic mucosal layer was separated from the muscle layer, and mucosal PGs levels were measured by high performance liquid chromatography. Four kinds of PGs, i.e., 6-keto-PG F1 alpha, PGF2 alpha, PGE2, and PGD2 were detected in gastric mucosa. Administration of 50% ethanol and water immersion stress induced gastric lesions and decreased all 4 mucosal PGs levels. Arbaprostil, 10 micrograms/kg, reduced ethanol-induced gastric lesions and maintained mucosal PGs levels, concomitantly, however, the same doses of arbaprostil did not show a protective effect against water immersion stress-induced gastric lesions or decreases in PGs levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

A multiclinic trial evaluating arbaprostil [15(R)-15-methyl prostaglandin E2] as a therapeutic agent for gastric ulcer.

A randomized, double-blind, placebo-controlled, multiclinic trial evaluated arbaprostil [15(R)-15 methyl prostaglandin E2] for the treatment of acute gastric ulcer, achieving an overall enrollment of 124 patients (of which 113 were considered evaluable). This 6-wk trial used an arbaprostil dose of 10 micrograms q.i.d., which has little gastric acid antisecretory activity. Endoscopies were performed after 21 and 42 days of treatment, at which times the arbaprostil and placebo healing rates, respectively, were 6/59 (10.2%) and 4/53 (7.6%) on day 21 and 25/59 (42.4%) and 16/50 (32.0%) on day 42. No significant differences between the treatment groups were found for pain relief, antacid consumption, and mucosal healing. This trial documents that a 10-micrograms dose of arbaprostil (which may be considered cytoprotective because of its small effect on gastric acid secretion), although safe and associated with no side effects, is not efficacious in healing acute gastric ulcers.

Effects of 15(S)-15-methyl prostaglandin E2 methyl ester on phospholipid metabolism in rat gastric mucosa.

The effects of 15(S)-15-methyl prostaglandin E2 (PGE2) methyl ester on gastric mucosal metabolism of phospholipids in intact rats and rats injured by intragastric instillation of acidified taurocholic acid were examined by using radioisotope-labeled precursors. The incorporation of palmitic, oleic and arachidonic acids into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was reduced by treatment with 15(S)-15-methyl PGE2 methyl ester in the intact rats, but the incorporation of glycerol was unaffected or affected only slightly. Instillation of acidified taurocholic acid resulted in decreased incorporation of palmitic acid and glycerol into PC and PE, whereas pretreatment with 15(S)-15-methyl PGE2 methyl ester caused the incorporations of these precursors to be maintained after acidified taurocholic acid treatment. These results suggest that 15(S)-15-methyl PGE2 methyl ester may reduce the incorporation of fatty acids into PC and PE by inhibition of the deacylation-reacylation cycle either directly or indirectly, whereas acidified taurocholic acid decreases de novo synthesis of PC and PE, and probably also the reacylation of fatty acid into phospholipids. Pretreatment with 15(S)-15-methyl PGE2 methyl ester protected the PC- and PE-synthesizing activity against the injury induced by acidified taurocholic acid, and this effect may be involved in the prevention of mucosal damage.

Effect of 15(R)-15-methyl PGE2 (arbaprostil) on duodenal bicarbonate secretion in rat.

The present study was designed to observe the effect of 15(R)-15-methyl PGE2 (arbaprostil) on duodenal bicarbonate secretion in male Wistar rats anesthetized with urethane. A proximal duodenal loop (1.5cm) was made and perfused with saline (pH4.5) in an air tight circle system. The pH and Pco2 of the perfusing fluid were measured continuously and the quantity of bicarbonate was calculated according to the Henderson-Hasselbalch equation. Vehicle or arbaprostil was injected intravenously as a bolus injection. The total output of bicarbonate in 30 min was as follows; control: 0.449 +/- 0.093 microEq (mean +/- SE); 1,10 and 100 mu/kg of arbaprostil: 0.752 +/- 0.218, 2.75 +/- 0.430 and 5.958 +/- 0.578 microEq respectively. Arbaprostil (10 and 100 micrograms/kg) increased the total output of bicarbonate significantly (p less than 0.001). The rate of secretion was also increased by arbaprostil.

Pregnancy interruption with RU 486 in combination with dl-15-methyl-prostaglandin-F2 alpha-methyl ester: the Chinese experience.

In a multicenter study taking place in four centers in Beijing (People's Republic of China), pregnancies up to 49 days of amenorrhea (DA) were interrupted with RU 486 (RU 38486, mifepristone, 600 mg orally once), followed 36-60 hours later by administration of dl-15-methyl-PGF 2 alpha-methyl ester (PG05, 1 mg vaginal suppository). One-hundred-and-sixty women were included in the study, three of whom being excluded from efficacy assessment because of non-compliance to the protocol. Complete pregnancy interruption without additional surgical procedure (success) was obtained in 136 women (86.6%, 95% confidence interval: 81.3-91.9%). The success rate was significantly (P = 0.013) higher for pregnancies below (91.3%), than for pregnancies above 42 days of amenorrhea (DA) (76.6%). The time elapsed between RU 486 intake and complete expulsion was 2.8 +/- 1.5 (sd) days (range: 1-12 days). Expulsion took place at the latest 4 days after RU 486 in 125 women (94.7%), and in 107 of these women, it occurred 3.1 +/- 1.7 (sd) hours after PG05 administration. Uterine bleeding occurred in all women after RU 486 intake whatever the outcome of treatment and lasted 11.5 +/- 4.8 (sd) days (range: 3-36 days). It was judged more or much more abundant than usual periods in 6.15% of the women. It led to a slight but significant decrease in hemoglobin as measured eight and 14 days after RU 486 intake. In five women, hemoglobin decreased by 4 g/dl or more, but no patient required a blood transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: In a multicenter study taking place across 4 centers in Beijing, People's Republic of China, pregnancies of up to 49 days of amenorrhea (DA) were interrupted with RU486 (RU 38486, mifepristone, 600 mg, orally once), followed 36-60 hours later by administration of dl-15-methyl-PGF2alpha-methyl ester (PGO5, 1 mg vaginal suppository). 166 women were included in this study; however, 3 were excluded from efficacy assessment because of noncompliance to the protocol. Complete pregnancy interruption without additional surgical procedure (success) was obtained in 136 women (86.6%, 95% confidence interval; 81.3-91.9%). The success rate was significantly (P=0.013) higher for pregnancies below 91.3%), than for pregnancies greater than 42 DA (76.6%). The time elapsed between RU486 intake and complete expulsion was 2.8 +or- 1.5 SD days (range 1-12 days). Expulsion took place at the latest 4 days after RU486 in 125 women (94.7%), and in 107 of these women, it occurred 3.1 +or- 1.7 SD hours after PGO5 administration. Uterine bleeding occurred in all women after RU486 intake, whatever the outcome of treatment, and latest 11.5 +or- 4.8 SD days (range 3-36 days). It was considered that 6.15% of the women had more or much more abundant bleeding. It led to a slight but significant decrease in hemoglobin as measured both 8 and 14 days after RU486 intake. In 5 women, hemoglobin decreased by 4 g/dl or more, but no patient required a blood transfusion. The clinical and biological tolerance of the treatment was otherwise very satisfactory--mild to moderate pain was reported in approximately 80% of the women after PGO5 administration, and in approximately 20% of the patients, nausea, vomiting, and diarrhea were observed. These were usually moderate, although in 1 case, severe vomiting occurred after RU486 intake and necessitated vacuum aspiration before PGO5 administration. A moderate and transient increase in SGPT (to less than 1.5 times the upper normal limit) was noted in 3 women after RU486 and before PGO5, and in 5 women after both.