Bupropion is widely used as an antidepressant drug and also as a smoking cessation aid. In humans, this drug is extensively metabolized to form several metabolites. Oxidised hydroxybupropion and two reduced metabolites, threohydrobupropion and erythrohydrobupropion, are major metabolites. All of these metabolites are considered to be active. Although the oxidative metabolic pathway and the central role of CYP2B6 are known, the enzymes that participate in the reduction have not been identified to date. The aim of this study was to confirm the role of human liver subcellular fractions in the metabolism of bupropion and elucidate the contribution of particular carbonyl-reducing enzymes. An HPLC method for the determination of bupropion metabolites was utilised. Bupropion is reduced to threohydrobupropion and less to erythrohydrobupropion in human liver cytosol, microsomes and also mitochondria. Surprisingly, intrinsic clearance for formation of both metabolites is the highest in mitochondrial fraction. Moreover this study provides the first direct evidence that 11β-hydroxysteroid dehydrogenase 1, AKR1C1, AKR1C2, AKR1C3 and CBR1 participate in the reducing biotransformation of bupropion in vitro. The enzyme kinetics of all of these reductases was investigated and kinetic parameters were calculated.

• MeSH
• alkoholoxidoreduktasy genetika   metabolismus   MeSH
• antidepresiva druhé generace metabolismus   MeSH
• biotransformace MeSH
• bupropion analogy a deriváty   metabolismus   MeSH
• cytosol enzymologie   MeSH
• hydroxysteroiddehydrogenasy genetika   metabolismus   MeSH
• jaterní mikrozomy enzymologie   MeSH
• jaterní mitochondrie enzymologie   MeSH
• játra enzymologie   MeSH
• kinetika MeSH
• lidé MeSH
• oxidace-redukce MeSH
• rekombinantní proteiny metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkoholoxidoreduktasy MeSH
• antidepresiva druhé generace MeSH
• bupropion MeSH
• CBR1 protein, human MeSH Prohlížeč
• hydrobupropion MeSH Prohlížeč
• hydroxysteroiddehydrogenasy MeSH
• rekombinantní proteiny MeSH