Role of transporter-mediated efflux in the placental biodisposition of bupropion and its metabolite, OH-bupropion

Cigarette smoking during pregnancy is a preventable risk factor associated with maternal and fetal complications. Bupropion is an antidepressant used successfully for smoking cessation in non-pregnant patients. Our goal is to determine whether it could benefit the pregnant patient seeking smoking cessation. The aim of this investigation was to determine the role of human placenta in the disposition of bupropion and its major hepatic metabolite, OH-bupropion. The expression of efflux transporters P-gp and BCRP was determined in placental brush border membrane (n = 200) and revealed a positive correlation (p < 0.05). Bupropion was transported by BCRP (K-t 3 mu M, V-max 30 pmol/mg protein/min) and P-gp (K-t 0.5 mu M, V-max 6 pmol/mg protein*min) in placental inside-out vesicles (IOVs). OH-bupropion crossed the dually-perfused human placental lobule without undergoing further metabolism, nor was it an efflux substrate of P-gp or BCRP. In conclusion, our data indicate that human placenta actively regulates the disposition of bupropion (via metabolism, active transport), but not its major hepatic metabolite, OH-bupropion. (C) 2010 Elsevier Inc. All rights reserved.