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Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
Published on: June 18, 2013
Bupropion metabolism by human placenta
Xiaoming Wang1, Doaa R Abdelrahman, Olga L Zharikova
1Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, 77555-0587, USA.
Biochemical Pharmacology
|January 30, 2010
Summary
Human placentas metabolize bupropion, a smoking cessation aid, into hydroxybupropion and other compounds. This placental metabolism, involving specific enzymes, is crucial for understanding bupropion
Area of Science:
- Pharmacology and Toxicology
- Reproductive Medicine
- Biochemistry
Background:
- Maternal smoking during pregnancy is a significant, modifiable risk factor for adverse pregnancy outcomes.
- Bupropion is a potential smoking cessation aid, but its use in pregnant individuals requires further investigation into its metabolic fate.
- Understanding bupropion's bio-disposition in pregnancy is essential for assessing its safety and efficacy.
Purpose of the Study:
- To investigate the metabolism of bupropion in human placental tissue.
- To identify bupropion metabolites formed in the placenta.
- To determine the enzymes responsible for bupropion metabolism and their reaction kinetics.
Main Methods:
- Incubation of bupropion with placental tissue from non-smoking and smoking women.
- Identification of bupropion metabolites using analytical techniques.
- Enzyme assays to identify the specific enzymes (e.g., CYP2B6, 11beta-hydroxysteroid dehydrogenases) involved in metabolism.
- Kinetic analysis of metabolite formation.
Main Results:
- Human placentas metabolized bupropion to hydroxybupropion, erythrohydrobupropion, and threohydrobupropion.
- Formation rates of erythro- and threohydrobupropion were significantly higher than hydroxybupropion.
- Metabolism exhibited saturation kinetics with an apparent K(m) of 40µM.
- 11beta-hydroxysteroid dehydrogenases were identified as major enzymes for bupropion reduction to erythro- and threohydrobupropion.
- CYP2B6 was identified as the primary enzyme responsible for hydroxybupropion formation.
Conclusions:
- Human placental tissue possesses enzymatic pathways for bupropion metabolism.
- Both carbonyl-reducing (11beta-hydroxysteroid dehydrogenases) and oxidizing (CYP2B6) enzymes contribute to bupropion's placental metabolism.
- These findings provide critical data for evaluating bupropion's use in pregnant smokers.
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