期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 74, 期 4, 页码 326-333出版社
WILEY
DOI: 10.1016/S0009-9236(03)00202-9
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Aim: Our objective was to study the effect of hormone replacement therapy and a combination oral contraceptive on the cytochrome P450 (CYP) 2B6 activity with bupropion (INN, amfebutamone) hydroxylation used as a probe reaction. Methods: This was a 3-way crossover study with 12 healthy female volunteers. The first phase was a control phase, in which all subjects received a single 150-mg dose of bupropion (sustained release) without pretreatment. In the second and third phases, in randomized balanced crossover order, subjects received a 10-day pretreatment with either hormone replacement therapy, containing 2 mg estradiol valerate and 250 mug levonorgestrel, or an oral contraceptive, containing 30 mug ethinyl estradiol (INN, ethinylestradiol) and 150 mug desogestrel, and the bupropion dose was given 1 hour after the last hormone dose. The bupropion, hydroxybupropion, and hydrobupropion plasma concentrations were determined for up to 72 hours. Results: The 10-day hormone replacement therapy pretreatment reduced the hydroxybupropion/bupropion area under the plasma concentration-time curve (AUC) ratio by 49% (P < .001; 95% confidence interval [CI], -58% to -40%) as a result of a marked 47% decrease (P < .001; 95% CI, -54% to -41%) in the AUC of hydroxybupropion. Moreover, the AUC of hydrobupropion was significantly (64%; P = .003; 95% CI, 22% to 106%) increased. The AUC of hydroxybupropion was also reduced after the oral contraceptive treatment but to a lesser extent (-31%; P < .001; 95% CI, -37% to -26%). However, the hydroxybupropion/ bupropion AUC ratio was not significantly affected. Conclusions: 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.
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