Disease relevance of TR-4698

• Rioprostil and duodenal ulcer [1].
• In addition, rioprostil prevented the weight loss which accompanied daily administration of aspirin (975 mg) in vehicle- or cimetidine-treated dogs [2].
• These results in animals suggest that clinically the use of antacid will not compromise the efficacy of rioprostil and that the combination may be a useful mode of therapy for the treatment of peptic ulcer disease [3].
• CsA blood and pancreatic tissue levels were not influenced by rioprostil at doses up to 120 micrograms/kb body weight [4].
• Antisecretory and antigastrin effects of rioprostil in gastric fistula dogs [5].

High impact information on TR-4698

• Night-time rioprostil versus ranitidine in duodenal ulcer healing [6].
• Subcutaneous injection of a new synthetic prostaglandin analogue Rioprostil 7.5 micrograms/kg bw twice daily completely prevented the effect of cyclosporin 5 mg/kg bw and protected significantly against the effects of cyclosporin 10 and 20 mg/kg bw [7].
• During the rioprostil period the effect of phenprocoumon on thrombotest and factor VII activities was significantly weaker (p less than 0.02, ANOVA) compared with the control experiment [8].
• Rioprostil, 7 days pretreatment, did not affect control parameters of blood coagulation activity [8].
• In separate studies, rioprostil had no effect on the sensitivity of the gastric mucosa to subsequent aspirin administration [2].

Chemical compound and disease context of TR-4698

• The efficacy and tolerability of the prostaglandin E1 derivative rioprostil (Bay o 6893) was studied in a randomized, double-blind, placebo-controlled trial in 40 patients affected by acute gastric ulcer [9].
• Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days [10].
• The efficacy and safety of the new prostaglandin E1 (PGE1) synthetic analogue, rioprostil, 300 micrograms b.d. and cimetidine, 400 mg b.d., on duodenal ulcer healing are compared in an international, multicentre, double-blind study [11].
• In nearly all trials natural prostaglandin E2 as well as the synthetic prostaglandin analogues arbaprostil, misoprostol, enprostil, rioprostil, trimoprostil, and rosaprostol accelerated the healing of peptic ulcers compared with placebo [12].

Biological context of TR-4698

• Additional studies determined that administration of rioprostil at doses of 720, 1440, or 2160 micrograms/kg/24 hr (935-2805 times the gastroprotective ED50 in 24 hr pumps) was well tolerated, with only slight, transient increases in body temperature, softening of the stools, and mild sedation at the highest dose [13].
• Pharmacokinetics of rioprostil in rats [14].
• The effects of rioprostil on gastric emptying and intragastric acidity [15].
• Thus, the metabolism of rioprostil proceeds via the biotransformation pathways of the naturally occurring prostaglandins [16].
• The influence of rioprostil on the resting pressure of the lower oesophageal sphincter (LESP) and on the bolus-stimulated contraction wave amplitude of primary peristalsis is investigated in 9 healthy male volunteers receiving placebo or 300 micrograms and 600 micrograms of rioprostil orally in a randomized, double-blind, threefold crossover study [17].

Anatomical context of TR-4698

• In 4-hr pylorus ligated rats, rioprostil inhibited gastric acid output when administered i.v., s.c., p.o. or intraduodenally, with ED50 values of 0.9, 1.8, 2.9 and 3.7 mg/kg, respectively [18].
• Effect of rioprostil and colchicine on CCl4-acute liver damage in rats. Relationship with plasma membrane lipids [19].
• The cytoprotective action of rioprostil on the pancreas may have therapeutic implications [20].
• Protective effect of rioprostil on indomethacin-induced lesions of gastric and duodenal mucosa in healthy volunteers [21].
• This may be due to an increase in the cytoprotective activity and to a decrease in the aggressive activity of the gastric juice by rioprostil [22].

Associations of TR-4698 with other chemical compounds

• This paper characterizes the ability of rioprostil, a synthetic primary alcohol prostaglandin E1 analog, to inhibit gastric acid secretion and prevent experimentally induced gastric lesions in rats and dogs, and determines the selectivity (the separation in potency) for these effects [18].
• Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P less than or equal to 0.001) and 45% (P less than or equal to 0.01), respectively, and both gave rise to an initial (approximately 10 min) delay of insulin and C-peptide responses, without a significant overall reduction in integrated incremental responses [23].
• In a double-blind crossover study, the gastric effects of a single oral dose of rioprostil (150 and 300 micrograms) or placebo were compared in basal conditions and during a 120-minute pentagastrin infusion [24].
• A preliminary analysis on a group of 182 patients participating in a large, multicentre trial comparing nocturnal rioprostil, 600 micrograms and ranitidine, 300 mg, is presented [25].
• In vitro experimental evidence suggests that the mechanism of the gastric antisecretory activity of rioprostil involves inhibition of the membrane bound histamine-stimulated adenylate cyclase [26].

Gene context of TR-4698

• Rioprostil administration, 300 micrograms twice daily resulted in a significant decrease of fasting insulin, C-peptide, glucagon, and pancreatic polypeptide [27].
• Basal serum gastrin levels and postprandial gastrin output are unchanged after treatment with rioprostil [28].
• Rioprostil, given in a dose of 100 micrograms b.i.d. to rats for 1 week significantly increases antral mucosal height but has no influence on the mucosal concentrations and cell densities of the gastric peptides, gastrin and somatostatin [28].
• The integrated 3-hour plasma gastrin response to the peptone meals was not significantly changed by any of the doses of rioprostil [29].
• In addition, in these rats rioprostil increased mucin levels and did not cause dermal irritation [30].

Analytical, diagnostic and therapeutic context of TR-4698

• Oral administration of dimethyl-PGE2 or rioprostil (25 and 50 micrograms/kg) prevented gastric ulceration significantly [31].
• This profile suggests that topical administration of rioprostil may be a useful means of delivery for clinical treatment of peptic ulcer disease [30].
• Rats received either CsA at a dose of 10 mg/kg body weight by tube feeding once in the morning, rioprostil at linearly increasing doses from 1.8 to 120 micrograms/kg body weight subcutaneously twice daily, a combination of both substances or NaCl [4].
• The effects of rioprostil (a newly developed synthetic prostaglandin E1 analogue) on meal-stimulated gastric acid secretion was evaluated in 8 healthy human volunteers [29].
• Treatment of duodenal ulcer with rioprostil: a randomized multicentre double-blind study [32].

References