• DOI:10.1111/J.1365-2125.1993.TB04161.X
• Corpus ID: 31232980

The metabolism of aprindine in relation to the sparteine/debrisoquine polymorphism.

@article{Ebner1993TheMO,
  title={The metabolism of aprindine in relation to the sparteine/debrisoquine polymorphism.},
  author={Thomas Ebner and Michel F Eichelbaum},
  journal={British journal of clinical pharmacology},
  year={1993},
  volume={35 4},
  pages={
          426-30
        }
}

• T. Ebner, M. Eichelbaum
• Published 1 April 1993
• Biology, Chemistry
• British journal of clinical pharmacology

1. Incubation of the class I antiarrhythmic drug aprindine (AP) with human liver microsomes resulted in the formation of two hydroxylated metabolites (HA1 and HA2) and desethylaprindine which were identified by GC-mass spectrometry. In liver microsomes isolated from a poor metaboliser (PM) of sparteine no hydroxylated metabolites of AP were detected whereas AP N-dealkylation was unimpaired. Thus hydroxylation of AP is mediated by cytochrome P450 2D6 (CYP2D6). 2. AP was found to be a competitive inhibitor of CYP2D6 as indicated by its ability to impair the formation of (2S)-hydroxysparteine, 5,6-didehydrosparteine and 5-hydroxypropafenone by human liver microsomes. 3. These in vitro findings are consistent with a major role of CYP2D6 in the clearance of AP in vivo, with its ability to impair the metabolism of other CYP2D6 substrates in vivo, and an ability to cause phenocopying (conversion of extensive metaboliser phenotypes for sparteine/debrisoquine to apparent 'poor metabolisers).