The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects

Br J Clin Pharmacol. 2003 Aug;56(2):232-7. doi: 10.1046/j.1365-2125.2003.01868.x.


Aims: To study the effect of an oral contraceptive (OC) formulation containing ethinyloestradiol and levonorgestrel (LNG) (combination OC) or LNG alone on the CYP2C19-mediated hydroxylation of omeprazole in healthy females.

Methods: This was an open crossover study with three phases. In phase one, 10 healthy females received a single 40-mg dose of omeprazole. Thereafter the subjects received in a random order either 40 micro g ethinyloestradiol and 75 micro g LNG or 60 micro g LNG alone once daily for 10 days. On day 10, 1 h after the last OC dose, subjects received a single 40-mg oral dose of omeprazole. The plasma concentrations of omeprazole, 5'-hydroxyomeprazole and omeprazole sulphone were determined for up to 8 h.

Results: The use of combination OC increased the area under the curve (AUC) of omeprazole by 38% [95% confidence interval (CI) - 3.8, 80; P = 0.040] and caused a 48% increase (95% CI 28, 68) in the AUC ratio of omeprazole/5-hydroxyomeprazole. LNG alone did not effect the 5'-hydroxylation of omeprazole. Neither of the OC preparations seemed to have an inhibitory effect on the formation of omeprazole sulphone by CYP3A4.

Conclusions: Oral contraceptives containing ethinyloestradiol but not those containing only LNG decrease CYP2C19 activity.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Enzyme Inhibitors / metabolism*
  • Female
  • Half-Life
  • Humans
  • Levonorgestrel / pharmacology*
  • Lynestrenol / pharmacology*
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Omeprazole / metabolism*


  • Contraceptives, Oral, Synthetic
  • Enzyme Inhibitors
  • Levonorgestrel
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Lynestrenol