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. 2010 May;23(5):409-16.
doi: 10.1080/14767050903168424.

Transplacental transfer and metabolism of bupropion

Angela D Earhart  1 , Svetlana Patrikeeva, Xiaoming Wang, Doaa Reda Abdelrahman, Gary D V Hankins, Mahmoud S Ahmed, Tatiana Nanovskaya
Affiliations

Transplacental transfer and metabolism of bupropion

Angela D Earhart et al. J Matern Fetal Neonatal Med. 2010 May.

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 microg/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.

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Conflict of interest statement

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Figures

Figure 1
Figure 1
Structure of bupropion and its metabolites. (1) Bupropion; (2) hydroxybupropion; (3) erythrohydrobupropion; (4) threohydrobupropion. Bupropion is biotransformed in human liver by: 1) hydroxylation of the tertiary-butyl chain to OH-bupropion and 2) by reduction of the carbonyl group giving rise to the two isomers threohydrobupropion and erythrohydrobupropion [30].
Figure 2
Figure 2
HPLC elution profiles of the standard compounds of bupropion and its metabolites. Figure 2A: HPLC elution profile of the standard compounds of bupropion and its metabolites as detected by UV at 254 nm. (1): hydroxybupropion (6.7 minutes), (2): erythrohydrobupropion (7.7 minutes), (3): threohydropbupropion (8.5 minutes), (4): bupropion (10.9 minutes). Figure 2B: HPLC elution profile of standard custom-synthesized [3H]-bupropion as detected by β-RAM-flow-through on-line detector. Figure 2C-F: Chromatograms of perfusion medium and tissue homogenate after 240 minutes of perfusion as detected by β-RAM flow-through on-line detector. (C): Maternal perfusate in absence of placenta. (D): Maternal perfusate in presence of placenta. (E): Fetal perfusate in presence of placenta. (F): Placental tissue homogenate. Two major peaks at 8.5 minutes and 10.9 minutes are detected in the maternal and fetal perfusate and placental tissue, corresponding to the metabolite (3) and parent drug (4).
Figure 3
Figure 3
Relative amounts of bound and free bupropion in maternal and fetal media in absence (3A) and presence (3B) of human serum albumin (HSA) following its perfusion for 4 hours. (3A) In media of the maternal circuit devoid of added HSA: 17 ± 17% of bupropion was bound and the remainder was free. In the fetal circuit, bupropion was in its free form. (3B) In presence of 30 mg/mL HSA (physiologic concentration) added to media of both maternal and fetal circuits: elution of bupropion in the void volume of the column increased to 24 ± 12% in the maternal circuit. In the fetal circuit, bupropion was eluted 11 ± 4% as bound fraction.
Figure 3
Figure 3
Relative amounts of bound and free bupropion in maternal and fetal media in absence (3A) and presence (3B) of human serum albumin (HSA) following its perfusion for 4 hours. (3A) In media of the maternal circuit devoid of added HSA: 17 ± 17% of bupropion was bound and the remainder was free. In the fetal circuit, bupropion was in its free form. (3B) In presence of 30 mg/mL HSA (physiologic concentration) added to media of both maternal and fetal circuits: elution of bupropion in the void volume of the column increased to 24 ± 12% in the maternal circuit. In the fetal circuit, bupropion was eluted 11 ± 4% as bound fraction.
Figure 4
Figure 4
Transplacental transfer of bupropion during 4 hours of perfusion. The decline in bupropion concentration in the maternal circuit was biphasic: a rapid decline in the initial 30 minutes, followed by a slower decline in the remaining 210 minutes.
Figure 5
Figure 5
Distribution of bupropion between the placental tissue, maternal and fetal circuits.
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