European Journal of Clinical Pharmacology

, Volume 35, Issue 6, pp 625–629

In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

  • L. J. Dowie
  • J. E. Smith
  • A. J. MacGilchrist
  • R. Fraser
  • J. W. Honour
  • J. L. Reid
  • C. J. Kenyon
Originals

DOI: 10.1007/BF00637598

Cite this article as:
Dowie, L.J., Smith, J.E., MacGilchrist, A.J. et al. Eur J Clin Pharmacol (1988) 35: 625. doi:10.1007/BF00637598

Summary

The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.

Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 β hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and α cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 α hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 α hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.

These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 β hydroxysteroid dehydrogenase, 17 α hydroxylase or 11 β hydroxylation; 21 hydroxylase activity may be marginally attenuated.

Key words

omeprazolecortisol synthesisurinary steroid metabolitescholesterol cleavage inhibitionadrenal steroidogenesis

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • L. J. Dowie
    • 1
  • J. E. Smith
    • 2
  • A. J. MacGilchrist
    • 3
  • R. Fraser
    • 1
  • J. W. Honour
    • 2
  • J. L. Reid
    • 3
  • C. J. Kenyon
    • 1
  1. 1.MCR Blood Pressure UnitWestern InfirmaryGlasgowUK
  2. 2.Chemical Pathology and Cobbold LaboratoriesMiddlesex Hospital Medical SchoolLondonUK
  3. 3.Department of Materia MedicaStobhill General HospitalGlasgowUK