Effects of FCE20700, a new PGE2 derivative, on gastric acid secretion and cytoprotective processes in man.
The pharmacodynamic effects of FCE20700, a new PGE2 derivative, have been investigated in 6 healthy volunteers given single intragastric (i.g.) and intraduodenal (i.d.) doses of 1 and 2 mg and placebo, according to a double-blind, within-subjects design. For 30-270 min following i.g. administration the effect of FCE20700 on peptone-stimulated gastric acid secretion (AS) was assessed by i.g. titration, and serum gastrin (G) levels were also determined. For the same period after i.d. dosing the effect of the compound on pentagastrin-stimulated AS and on mucoproteins and bicarbonate content in the gastric juice was measured. Blood pressure (BP), heart rate and possible side-effects were monitored. Following i.g. administration there was a moderate, dose-related, significant inhibition of AS; significant inhibition of G levels was observed only after the highest dose. After i.d. administration there was a very modest though dose-related and significant inhibition of AS; a brief maximal increase in mucoproteins and in bicarbonate levels was apparent after the 1 mg dose. After i.d. but not after i.g. administration of 2 mg there was a modest but significant decrease in BP. No side-effects of clinical relevance were reported. The results appear to suggest a major activity of FCE20700 on cytoprotection rather than in inhibiting gastric acid secretion. The observed change in BP may indicate that after i.d. administration there will be some systemic effects of FCE20700.
D000328:Adult; D001639:Bicarbonates / Q000032:analysis; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D005744:Gastric Acid / Q000378:metabolism*; D005750:Gastric Juice / Q000032:analysis / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology; D005755:Gastrins / Q000032:analysis; D006801:Humans; D007441:Intubation, Gastrointestinal; D008297:Male; D009088:Mucoproteins / Q000032:analysis; D010418:Pentagastrin / Q000494:pharmacology; D010461:Peptones / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000009:adverse effects / Q000494:pharmacology*
D001639:Bicarbonates; D005755:Gastrins; D009088:Mucoproteins; D010461:Peptones; D011459:Prostaglandins E, Synthetic; C040808:FCE 20700; D010418:Pentagastrin; D015232:Dinoprostone