Gastric acid inhibitory profile of saviprazole (HOE 731) compared to omeprazole.
Saviprazole (HOE 731), a substituted thienoimidazole, caused a dose-dependent inhibition of gastric acid secretion in dogs and rats with ID50 values which were not significantly different from that of omeprazole indicating that both compounds are equally effective. The duration of action in dogs lasted for more than 24 h and was dependent on the state of stimulation. Measurement of serum concentrations of 1 mg/kg saviprazole after intravenous or intraduodenal administration revealed a bioavailability of about 60% in dogs. The elimination half-life was about 30 min following both routes of administration. In rats basal acid secretion was inhibited by saviprazole. In addition stimulation of acid secretion by histamine, desglugastrin, carbachol and isobutylmethylxanthine-forskolin was equally inhibited. This was in agreement with the known mechanism of action, inhibition of the gastric proton pump which is the last step of acid secretion within the parietal cell. Surprisingly, at high dose levels, saviprazole differed from omeprazole. After saviprazole, 1 mg/kg i.v. to dogs, acid output dropped to zero but recovered within 30 min to a level of 90%, whereas omeprazole depressed acid output completely over the whole observation period (4.5 h). Similar results were obtained in pylorus-ligated rats.
Herling
A W
AW
Hoechst, Frankfurt/Main, FRG.
Scholl
T
T
Bickel
M
M
Lang
H J
HJ
Scheunemann
K H
KH
Weidmann
K
K
Rippel
R
R
D000818:Animals; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D016623:Ion Pumps / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010477:Perfusion; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000494:pharmacology*; D005466:Fluorocarbons
D007093:Imidazoles; D016623:Ion Pumps; D009853:Omeprazole; D011522:Protons; D013876:Thiophenes; C067765:Hoe 731; D005466:Fluorocarbons