Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man.

Abstract

SUMMARY The effects of omeprazole, a substituted benzimidazole, on gastric acid and pepsin secretion have been studied in twelve healthy subjects. From six to eight hours after a single oral dose of 30 mg, there was a 66% reduction in basal acid output, and a 71*2% reduction in pentagastrin stimulated acid output. A single dose of 60 mg produced a 91.7% reduction in basal acid output and a 95-3% reduction in pentagastrin stimulated acid output. After seven days treatment with 30 or 60 mg daily, there was almost 100% inhibition of both basal and pentagastrin stimulated acid output. Omeprazole did not significantly affect pepsin secretion which is in keeping with its proposed mode of action, as an inhibitor of the H+/K+-ATPase enzyme on the secretory membrane of the parietal cell. There were no side effects after omeprazole either with single or repeated dosing.The substituted benzimidazoles are new agents which are potent inhibitors of gastric acid secretion. They act by selective, non-competitive inhibition of the H+/K+-ATPase enzyme in the parietal cell.' This enzyme is the active transport mechanism for hydrogen ion secretion in the stomach. Although one of these agents, omeprazole, has been shown to suppress basal and pentagastrin stimulated acid secretion after a single dose,2 little is known about its effects after repeated dosing. In addition, previous studies have used a buffered suspension of the drug2 as it is partially inactivated by gastric acid, or have looked at its acid inhibitory effect 24 hours after a dose.3We have studied the effects of two different doses of omeprazole on basal and pentagastrin stimulated acid and pepsin secretion after a single dose and after seven days of treatment. Capsules of entericcoated omeprazole granules were used, and the effects studied around the time of expected maximum acid inhibition. Methods SUBJECTSTwelve healthy male subjects, mean age 25-2 years

Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man.

“…We have again demonstrated an increase in antisecretory effect with repeated dosing, accompanied by a rise in the systemic availability of omeprazole as reflected by an increase in AUC in all subjects. As omeprazole is acid-labile (Lind et al, 1983;Howden et al, 1984a) it is probable that the fraction absorbed is increased when there is suppression of acid secretion. When 15 mg omeprazole was given for 5 days the 30% in- ±5.4 ±26 ±6.7 ± 9.5 ± 52 *P < 0.02, **P 0.01, paired t-test.…”

“…We have previously reported on the antisecretory action of 30 and 60 mg in healthy subjects (Howden et al, 1984a (Lind et al, 1983;Howden et al, 1984a). We have therefore examined the pharmacokinetics of omeprazole and its effect on gastric secretion using a lower dose, 10 mg, given for 7 days.…”

“…Omeprazole was administered as capsules of enteric-coated granules; placebo capsules were identical in appearance, and subjects were unaware as to whether they were receiving drug or placebo. BAO was measured from 6 to 7 h from drug administration; PAO was measured from 7 to 8 h in response to pentagastrin 1.2 ,g kg-l according to methods previously described (Howden et al, 1984a). Volume of gastric secretion was recorded and aliquots were taken for determination of pepsin content (Berstad, 1975).…”

Effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion in rats.

“…The doses of omeprazole used in our study are considerably higher than the doses known to produce nearly complete inhibition of acid secretion for 24 hr in man (Howden et al 1984). Investigation of the antisecretory effect of omeprazole after single dose administration in rats showed that the antisecretory effect was not so long in rat as in man and dog (Howden et al 1984). Our study demonstrates that it is possible to inhibit gastric acid secretion effectively for 24 hr in rats with a single dose of omeprazole.…”

“…This results in a long-acting inhibitory effect on acid secretion as shown in this study, where acid secretion was inhibited by 85-90% 22-24 hr after 580,umole/kg x day of omeprazole. The doses of omeprazole used in our study are considerably higher than the doses known to produce nearly complete inhibition of acid secretion for 24 hr in man (Howden et al 1984). Investigation of the antisecretory effect of omeprazole after single dose administration in rats showed that the antisecretory effect was not so long in rat as in man and dog (Howden et al 1984).…”