Transplacental transfer and metabolism of bupropion

Abstract

Objective. In order to evaluate the potential use of bupropion as smoking cessation therapy during pregnancy, the aim of this investigation was to determine transplacental transfer and metabolism of bupropion and its distribution among placental tissue and maternal and fetal circuits of the dually perfused placental lobule.

Methods. Placentas obtained from healthy term pregnancies were perfused with bupropion at two concentrations 150 ng/ml and 450 ng/ml, along with the marker compound antipyrine 20 μg/ml. Radioactive isotopes of the two drugs were co-transfused to enhance their detection limits. Concentrations of bupropion and its metabolite were determined by liquid chromatography and liquid scintillation spectrometry.

Results. The fetal/maternal concentration ratio of bupropion was 1.07 ± 0.22. Following 4 h of its perfusion, 48 ± 6% of bupropion was retained by placental tissue, 32 ± 5% remained in the maternal circuit, and 20 ± 6% was transferred to the fetal circuit. A metabolite of bupropion, threohydrobupropion, was identified.

Conclusions. Bupropion was transferred from the maternal to fetal circuit and was biotransformed by placental tissue enzymes to its metabolite threohydrobupropion. Bupropion and its metabolite did not affect placental tissue viability or functional parameters. These data suggest that bupropion has the potential of being used for smoking cessation during pregnancy and should be further investigated for its safety and efficacy.

Keywords:

• Bupropion
• transplacental transfer
• metabolism
• smoking cessation
• pregnant smokers

Acknowledgements

The authors sincerely appreciate the support of the physicians and nurses of the Labor & Delivery Ward of the John Sealy Hospital, the teaching hospital at UTMB, Galveston, Texas, and the Perinatal Research Division of the Department of Obstetrics & Gynecology. The authors greatly appreciate the Publication, Grant, & Media Support area of the Department of Obstetrics & Gynecology. This work was supported by a NIDA grant RO1DA024094 to TN.