Inhibition by omeprazole of adrenocortical response to ACTH: clinical studies and experiments on bovine adrenal cortex in vitro.
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 mitochondrial cytochrome P-450 dependent hydroxylation reactions. In a double-blind placebo-controlled crossover 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 less than 0.005). In vitro, omeprazole caused a concentration-dependent inhibition of ACTH-stimulated cortisol release from isolated bovine adrenal cells (ED50 = 20 micrograms/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 11 beta-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.
D000302:Adrenal Cortex / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002417:Cattle; D002986:Clinical Trials as Topic; D003350:Cortodoxone / Q000096:biosynthesis; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009853:Omeprazole
D001562:Benzimidazoles; D000324:Adrenocorticotropic Hormone; D009853:Omeprazole; D003350:Cortodoxone; D006854:Hydrocortisone