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Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19
Author(s) -
Bertilsson Leif,
Tybring Gunnel,
Widén Jolanta,
Chang Ming,
Tomson Torbjörn
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00630.x
Subject(s) - omeprazole , cyp2c19 , hydroxylation , cyp3a4 , carbamazepine , pharmacology , chemistry , medicine , cytochrome p450 , metabolism , biochemistry , epilepsy , enzyme , psychiatry
Aims 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.