Inhibition by omeprazole of adrenocortical response to ACTH

clinical studies and experiments on bovine adrenal cortex in vitro

Colin Howden, C. J. Kenyon, G. H. Beastall, J. L. Reid

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Omeprazole, a substituted benzimidazole, is a potent inhibitor of gastric acid secretion which is currently being evaluated in patients with peptic ulcer and Zollinger-Ellison syndrome. Drugs which possess an imidazole nucleus have previously been shown to inhibit cortisol release from the adrenal cortex, secondary to inhibition of mitochrondrial cytochrome P-450 dependent hydroxylation reactions. In a double-blind placebo-controlled cross-over study in healthy male volunteers, omeprazole (60 mg daily for 7 days) did not alter basal cortisol levels. The peak cortisol response to ACTH stimulation was significantly reduced. Cortisol levels 60 min after ACTH were 824 ± 27 nmol/l on omeprazole (mean ± SEM), and 929 ± 35 on placebo (P < 0.005). In vitro, omeprazole caused a concentration-dependent inhibition of ACHT-stimulated cortisol release from isolated bovine adrenal cells (ED50 = 20 μg/ml). This was associated with a decrease in deoxycortisol synthesis. Therefore, unlike some other imidazole-containing drugs, the inhibitory effects of omeprazole are not entirely due to steroid 11β-hydroxylase inhibition. Substantial inhibition occurred at omeprazole concentrations which are higher than plasma levels normally achieved in clinical use. However, impairment of adrenocortical function may occur in patients on long-term high dose omeprazole treatment for Zollinger-Ellison syndrome.

Original languageEnglish (US)
Pages (from-to)99-102
Number of pages4
JournalClinical Science
Volume70
Issue number1
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

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Omeprazole
Adrenal Cortex
Adrenocorticotropic Hormone
Hydrocortisone
Zollinger-Ellison Syndrome
Steroid 11-beta-Hydroxylase
Placebos
Gastric Acid
Hydroxylation
Clinical Studies
In Vitro Techniques
Peptic Ulcer
Pharmaceutical Preparations
Cross-Over Studies
Cytochrome P-450 Enzyme System
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Inhibition by omeprazole of adrenocortical response to ACTH : clinical studies and experiments on bovine adrenal cortex in vitro. / Howden, Colin; Kenyon, C. J.; Beastall, G. H.; Reid, J. L.

In: Clinical Science, Vol. 70, No. 1, 01.01.1986, p. 99-102.

Research output: Contribution to journalArticle

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