TY - JOUR
T1 - Role of transporter-mediated efflux in the placental biodisposition of bupropion and its metabolite, OH-bupropion
AU - Hemauer, Sarah J.
AU - Patrikeeva, Svetlana L.
AU - Wang, Xiaoming
AU - Abdelrahman, Doaa R.
AU - Hankins, Gary
AU - Ahmed, Mahmoud
AU - Nanovskaya, Tatiana N.
N1 - Funding Information:
The authors thank the Perinatal Research Division for their assistance, and the Publication, Grant, & Media Support of the UTMB Department of Obstetrics and Gynecology . Supported by the National Institute on Drug Abuse Grant R01DA024094 to TN.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/10
Y1 - 2010/10
N2 - 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 (Kt 3μM, Vmax 30pmol/mg protein/min) and P-gp (Kt 0.5μM, Vmax 6pmol/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.
AB - 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 (Kt 3μM, Vmax 30pmol/mg protein/min) and P-gp (Kt 0.5μM, Vmax 6pmol/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.
KW - Breast cancer resistance protein
KW - Bupropion
KW - P-Glycoprotein
KW - Placenta
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=77955654070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955654070&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2010.06.025
DO - 10.1016/j.bcp.2010.06.025
M3 - Article
C2 - 20599802
AN - SCOPUS:77955654070
SN - 0006-2952
VL - 80
SP - 1080
EP - 1086
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 7
ER -