Metabolism of bupropion by baboon hepatic and placental microsomes

Xiao-Ming Wang, Doaa R. Abdelrahman, Valentina Fokina, Gary Hankins, Mahmoud Ahmed, Tatiana Nanovskaya

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 μM, Vmax 258 ± 32 pmol mg protein-1 min-1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalBiochemical Pharmacology
Volume82
Issue number3
DOIs
StatePublished - Aug 1 2011

Fingerprint

Bupropion
Papio
Microsomes
Metabolism
Liver
Oxidoreductases
Biotransformation
Alcohol Oxidoreductases
Flufenamic Acid
Glycyrrhetinic Acid
11-beta-Hydroxysteroid Dehydrogenases
Ticlopidine
Vitamin K 3
Phencyclidine
Metabolites
Isoenzymes
Monoclonal Antibodies
hydroxide ion
Kinetics
hydrobupropion

Keywords

  • Baboon
  • Bupropion
  • Liver
  • Metabolism
  • Placenta

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Metabolism of bupropion by baboon hepatic and placental microsomes. / Wang, Xiao-Ming; Abdelrahman, Doaa R.; Fokina, Valentina; Hankins, Gary; Ahmed, Mahmoud; Nanovskaya, Tatiana.

In: Biochemical Pharmacology, Vol. 82, No. 3, 01.08.2011, p. 295-303.

Research output: Contribution to journalArticle

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