Hormone replacement therapy markedly inhibited the CYP2B6-catalyzed hydroxylation of bupropion, whereas a combination oral contraceptive had only a modest effect on CYP2B6 activity. Patients receiving hormone replacement therapy or oral contraceptives may need dose adjustment when treated with drugs metabolized by CYP2B6.

Aims To characterize the effect of an oral contraceptive (OC) containing ethinylestradiol and gestodene on the activity of CYP3A4 in vivo as measured by the 1k-hydroxylation of midazolam. Methods In this randomised, double-blind, cross-over trial nine healthy female subjects received either a combined OC (30 mg ethinylestradiol and 75 mg gestodene) or placebo once daily for 10 days. On day 10, a single 7.5 mg dose of midazolam was given orally. Plasma concentrations of midazolam and 1k-hydroxymidazolam were determined up to 24 h and the effects of midazolam were measured with three psychomotor tests up to 8 h. Results The combined OC increased the mean AUC of midazolam by 21% (95% CI 2% to 40%; P=0.03) and decreased that of 1k-hydroxymidazolam by 25% (95% CI 10% to 41%; P=0.01), compared with placebo. The metabolic ratio (AUC of 1k-hydroxymidazolam/AUC of midazolam) was 36% smaller (95% CI 19% to 53%; P=0.01) in the OC phase than in the placebo phase. There were no signi®cant differences in the C max , t max , t K or effects of midazolam between the phases. Conclusions A combined OC preparation caused a modest reduction in the activity of CYP3A4, as measured by the 1k-hydroxylation of midazolam, and slightly increased the AUC of oral midazolam. This study suggests that, at the doses used, ethinylestradiol and gestodene have a relatively small effect on CYP3A4 activity in vivo.

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. MethodsThis 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 m g ethinyloestradiol and 75 m g LNG or 60 m 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.