The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects.
OBJECTIVE
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.
Palovaara
Sanna
S
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland. sanna.palvovaara@utu.fi
Tybring
Gunnel
G
Laine
Kari
K
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D008234:Lynestrenol / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009853:Omeprazole / Q000378:metabolism*
D003280:Contraceptives, Oral, Synthetic; D004791:Enzyme Inhibitors; D016912:Levonorgestrel; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D008234:Lynestrenol