Gastric acid inhibitory profile of ebrotidine, a novel H2-receptor antagonist in humans.
This study was designed to assess the gastric secretory effects of ebrotidine, a novel H2 receptor antagonist, in humans. Three groups (A, B and C) of male subjects with normal gastric mucosa were used. Group A (6 subjects) was used to determine the dose-dependency of gastric inhibitory effect of ebrotidine on basal and pentagastrin-induced maximal acid output. Group B (8 subjects) was employed to examine the duration of the inhibitory effect of ebrotidine on basal and pentagastrin-induced acid secretion. In group C (6 subjects), the 24h pH-metry was assessed using intraluminal pH-electrode placed in the gastric corpus and connected to a portable recording unit. Single oral dose of ebrotidine (200, 400 or 800 mg) caused a dose-dependent reduction in basal and pentagastrin-induced acid secretion that at a dose of 800 mg amounted to about 89% and 93%, respectively. This inhibition was still observed after 6h and averaged 72% and 50%, respectively. After 12 and 24h upon the drug intake, both basal and pentagastrin-induced acid secretion returned to the control values. Single oral dose of ebrotidine (800 mg) caused a significant reduction in circadian acidity and resulted in a marked and significant reduction of intragastric acidity for about 6h upon the administration. This inhibition was accompanied by a transient increase in basal and postprandial gastrin levels. We conclude that ebrotidine is highly effective inhibitor of basal, pentagastrin-induced and circadian gastric acid secretion in humans.
Institute of Physiology, Univ. Medical School, Krakow, Poland.
M
M
Maczka
N
N
Kwiecień
W
W
Obtułowicz
S J
SJ
Konturek
K
K
Kamiński
J
J
Oleksy
A
A
Gabryelewicz
J
J
Torres
D000284:Administration, Oral; D000328:Adult; D000863:Antacids / Q000008:administration & dosage / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008954:Models, Biological; D010919:Placebos; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000863:Antacids; D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D010919:Placebos; D013844:Thiazoles; C075156:ebrotidine