Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, 77555-0587, USA.
Biochem Pharmacol. 2010 Jun 1;79(11):1684-90. doi: 10.1016/j.bcp.2010.01.026. Epub 2010 Jan 28.
Smoking during pregnancy is the largest modifiable risk factor for pregnancy-related morbidity and mortality. The success of bupropion for smoking cessation warrants its investigation for the treatment of pregnant patients. Nevertheless, the use of bupropion for the treatment of pregnant smokers requires additional data on its bio-disposition during pregnancy. Therefore, the aim of this investigation was to determine the metabolism of bupropion in placentas obtained from nonsmoking and smoking women, identify metabolites formed and the enzymes catalyzing their formation, as well as the kinetics of the reaction. Data obtained revealed that human placentas metabolized bupropion to hydroxybupropion, erythro- and threohydrobupropion. The rates for formation of erythro- and threohydrobupropion exceeded that for hydroxybupropion by several folds, were dependent on the concentration of bupropion and exhibited saturation kinetics with an apparent K(m) value of 40microM. Human placental 11beta-hydroxysteroid dehydrogenases were identified as the major carbonyl-reducing enzymes responsible for the reduction of bupropion to threo- and erythrohydrobupropion in microsomal fractions. On the other hand, CYP2B6 was responsible for the formation of OH-bupropion. These data suggest that both placental microsomal carbonyl-reducing and oxidizing enzymes are involved in the metabolism of bupropion.
怀孕期间吸烟是导致与妊娠相关的发病率和死亡率的最大可改变风险因素。安非他酮在戒烟方面的成功为其治疗妊娠患者的应用提供了依据。然而，安非他酮在治疗妊娠吸烟者中的应用需要更多关于其在妊娠期间生物分布的数据。因此，本研究旨在确定从不吸烟和吸烟的女性中获得的胎盘对安非他酮的代谢情况，鉴定形成的代谢物及其形成的酶，并确定反应动力学。研究结果表明，人胎盘将安非他酮代谢为羟基安非他酮、赤式-和苏式-羟基安非他酮。赤式-和苏式-羟基安非他酮的形成率是羟基安非他酮的数倍，依赖于安非他酮的浓度，表现出饱和动力学，表观 K(m)值为 40μM。人胎盘 11β-羟甾脱氢酶被鉴定为主要的羰基还原酶，负责将安非他酮还原为苏式和赤式羟基安非他酮。另一方面，CYP2B6 负责形成 OH-安非他酮。这些数据表明，胎盘微粒体羰基还原酶和氧化酶都参与了安非他酮的代谢。
