Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine

Eur J Clin Pharmacol. 1989;37(2):155-60. doi: 10.1007/BF00558224.


On separate occasions 6 extensive metabolizers of sparteine took a single oral dose of 100 mg imipramine and desipramine before and during the intake of quinidine sulphate 200 mg/day. During quinidine the total oral clearance of imipramine on average was reduced by 35%, and that of desipramine by 85%. The clearance of imipramine via demethylation was not significantly reduced during quinidine administration, whereas its clearance by other pathways, largely 2-hydroxylation, was reduced by more than 50%. 2-OH-Imipramine and 2-OH-desipramine were detected in plasma before (maximum concentrations 30-100 nmol.l-1) but not during quinidine. It appears that quinidine is a potent inhibitor of the sparteine/debrisoquine oxygenase, P450dbl, which is responsible for the 2-hydroxylation of imipramine and desipramine, but not of the P450 isozyme responsible for the demethylation of imipramine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dealkylation
  • Desipramine / analogs & derivatives
  • Desipramine / metabolism*
  • Desipramine / pharmacokinetics
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Hydroxylation
  • Imipramine / metabolism*
  • Imipramine / pharmacokinetics
  • Male
  • Phenotype
  • Quinidine / pharmacology*
  • Sparteine / metabolism


  • Sparteine
  • Quinidine
  • Imipramine
  • Desipramine
  • 2-hydroxydesipramine