Pharmacokinetics and metabolism of omeprazole in animals and man - an overview

Regårdh, C G; Gabrielsson, M; Hoffman, Kyle; Löfberg, Ida; Skånberg, Inger

doi:10.3109/00365528509095821

Cited by 126 publications

(58 citation statements)

References 10 publications

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“…In contrast, the gastroprotective effect of oral omeprazole used as a reference drug was completely attenuated by the same treatment, and this result is consistent with the previous reports (18,19). Since omeprazole is readily degraded by acidic pH (20), the degraded compounds produced in the gastric juice of the lumen are considered to exert the gastroprotective effect by a local action from the luminal side. Therefore, omeprazole loses the ability to exert a gastroprotective effect in the absence of luminal acid.…”

Section: Studies Of the Gastroprotective Mechanisms Of Frg-8813supporting

confidence: 82%

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Onodera

Shibata

Tanaka

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-FRG-8813 ((±)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2-butenyl]acetamide) is a novel histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activities. The present study was designed to investigate the property of gastroprotective action. The oral ED50 values for inhibition of mucosal lesions against 1076 NH3-, 60% ethanol in 0.15 N HCl-, 100% ethanol-, 0.6 N HCl-and sodium taurocholate in 0.4 N HCl-induced damage were 3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective despite pretreatment with omeprazole, suggesting that the protective effect is independent of its antisecretory activity. It is unlikely that FRG-8813 works as a mild irritant because it showed a gastroprotective effect after intraperitoneal injection, but oral administration itself did not influence the rat gastric mucosa. Although pretreatment with indomethacin or N-ethylmaleimide did not affect the gastroprotection of FRG-8813, chemical deafferentation induced by capsaicin abolished the gastroprotection.Furthermore, prior administration of tetrodotoxin, the calcitonin generelated peptide (CGRP) antagonist hCGRP8_37 or N~-nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither enhanced the susceptibility of the mucosa to damage nor affected the gastroprotective action of short-term treatment. In conclusion, these results suggest that FRG-8813 has gastroprotective activity independently of acid antisecretory activity and that capsaicin-sensitive nerves may be partially or fully involved in the gastroprotective mechanisms of FRG-8813. Keywords:FRG-8813, Gastroprotection, Histamine H2-receptor antagonist, Capsaicin-sensitive nerve, Antiulcer drug Successful peptic ulcer therapy depends on the restoration of the compromised integrity of the gastroduodenal mucosa by either reducing the aggressive factors or enhancing the defensive process in the mucosa. This has been mainly accomplished by reducing intraluminal acid with an histamine H2-receptor antagonist for more than 10 years. The histamine H2-receptor antagonists are among the most frequently employed drugs worldwide, and their leading position can be explained by their proven high antisecretory potency (1, 2). However, numerous reports showed that the incidence of ulcer relapse after discontinuation of the histamine H2-receptor antagonist reaches the same level as that in patients receiving a placebo (3 -5). From these viewpoints, further improvement in ulcer therapy, with regard to quality of ulcer healing and/or ulcer relapse, might be achieved if the agent could enhance the mucosal defensive capacity in addition to decreasing gastric acid secretion.The property of agents that protect the gastric mucosa against necrotizing agents such as ethanol was defined as so-called "cytoprotection"by Robert et al. (6). Subsequent observations demonstrated that although the gastric cells localized deep in the mu...

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Section: Studies Of the Gastroprotective Mechanisms Of Frg-8813supporting

confidence: 82%

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Onodera

Shibata

Tanaka

et al. 1995

Japanese Journal of Pharmacology

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“…Omeprazole is readily degraded by acidic pH or metabolized in the body resulting in omeprazole-sulfone or omeprazole-sulfide (20). Since NC-1300 was given p.o.…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective Effects of NC-1300 and Omeprazole on HCl⋅Ethanol-Induced Gastric Lesions in Rats

Okabe¹,

Awane²

1986

Japanese Journal of Pharmacology

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“…Regârdh et al [7] reported that the mean sys temic availability of a buffered oral solution of omeprazole increased with dosage, being 40.3, 53.6, 58.2 and 96.9% with doses of 10, 20, 40 and 90 mg, respectively. Saturation of first-pass metabolism at higher doses was suggested as a reason for this increase.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Omeprazole: Pharmacology, Pharmacokinetics and Interactions

Oosterhuis¹,

Jonkman²

1989

Digestion

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Omeprazole is a prodrug which is converted to its active form only at the site of action, namely the parietal cell. There it binds irreversibly with H⁺-K⁺-ATPase (the gastric proton pump), which causes an effective and long-lasting inhibition of gastric acid secretion. The pharmacokinetic profile of omeprazole is rather complicated, showing concentration-dependent elimination kinetics and an oral bioavailability which increases with the dose and during repeated administration. For the choice of dosage regimens this has minor consequences, in view of the wide therapeutic range of omeprazole and because an almost continuous maximum effect is obtained with once daily oral administration of 20–40 mg. Omeprazole may influence the pharmacokinetics of concurrently administered drugs by an inhibition of their oxidative metabolism. For most drugs studied thus far, the influence is less or even negligible in comparison with the influence of cimetidine, with the exception of diazepam. For every new combination of omeprazole with a drug that has a critical therapeutic range the consequences of a possible interaction should be studied.

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Pharmacokinetics and metabolism of omeprazole in animals and man - an overview

Cited by 126 publications

References 10 publications

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

Cytoprotective Effects of NC-1300 and Omeprazole on HCl⋅Ethanol-Induced Gastric Lesions in Rats

Omeprazole: Pharmacology, Pharmacokinetics and Interactions

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