CARBAMAZEPINE TREATMENT INDUCES THE CYP3A4 CATALYZED SULFOXIDATION OFOMEPRAZOLE, BUT HAS NO OR LESS EFFECT ON HYDROXYLATION VIA CYP2C19

Aims Omeprazole has been shown previously to be metabolized by the two cytochrome P450 isoforms CYP2C19 (hydroxylation) and CYP3A4 (sulphoxi dation). The objective of this study was to test the inducibility of t hese enzymes by carbamazepine (CBZ). Methods Omeprazole was given as a single oral dose before and after 3 weeks of treatment of five patien ts with CBZ (400-600 mg daily). Results Mean area under the plasma con centration VS time curve (AUC) between 0 and 8 h after drug intake, de creased by about 40% for omeprazole and its hydroxy metabolite and inc reased for its sulphone metabolite, but the changes were not statistic ally 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 significa nt decrease in the mean ratio of the AUC of the hydroxy and sulphone m etabolites from 2.58 to 0.93 (P = 0.046) with a mean difference of 1.7 9 (95% CI: 0.07 to 3.50) showing that the induction was more pronounce d 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.