Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19.
OBJECTIVE
Omeprazole has been shown previously to be metabolized by the two cytochrome P450 isoforms CYP2C19 (hydroxylation) and CYP3A4 (sulphoxidation). The objective of this study was to test the inducibility of these enzymes by carbamazepine (CBZ).


METHODS
Omeprazole was given as a single oral dose before and after 3 weeks of treatment of five patients with CBZ (400-600 mg daily).


RESULTS
Mean area under the plasma concentration vs time curve (AUC) between 0 and 8 h after drug intake, decreased by about 40% for omeprazole and its hydroxy metabolite and increased for its sulphone metabolite, but the changes were not statistically significant. The ratio of the AUCs of omeprazole and its sulphone, used as an index of CYP3A4 activity, decreased in all patients (P = 0.052), while there was no change in the omeprazole/hydroxyomeprazole AUC ratio used as an index for CYP2C19 activity. There was a significant decrease in the mean ratio of the AUC of the hydroxy and sulphone metabolites from 2.58 to 0.93 (P = 0.046) with a mean difference of 1.79 (95% CI: 0.07 to 3.50) showing that the induction was more pronounced for CYP3A4 than for CYP2C19.


CONCLUSIONS
CBZ induces CYP3A4, but not, or to a lesser extent, CYP2C19. The induction of the sulphoxidation of omeprazole by CBZ seems to have no major clinical implication.
Bertilsson
L
L
Department of Medical Laboratory Sciences and Technology at Karolinska Institutet, Huddinge Hospital, Sweden.
Tybring
G
G
Widén
J
J
Chang
M
M
Tomson
T
T
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D009853:Omeprazole / Q000493:pharmacokinetics*; D013454:Sulfoxides / Q000378:metabolism*
D000927:Anticonvulsants; D013454:Sulfoxides; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole