The N-demethylation of imipramine correlates with the oxidation of S-mephenytoin (S/R-ratio). A population study

Br J Clin Pharmacol. 1993 Mar;35(3):331-4.

Abstract

The metabolism of imipramine was investigated in 106 healthy volunteers, all having a sparteine metabolic ratio (MR) of 0.2-0.5 and hence classified as extensive metabolisers. Each subject was given a single oral dose of 25 mg imipramine hydrochloride and blood for assays of imipramine and metabolites was collected 3 h thereafter. The desipramine/imipramine ratio and the 2-OH-desipramine/2-OH-imipramine ratio in plasma, reflecting the demethylation of imipramine and 2-OH-imipramine, respectively, showed significant negative correlations with the mephenytoin S/R ratio (Spearman rank correlation) (rs): -0.46, P < 0.00002 and -0.41, P < 0.00002). No correlations were found between the 2-hydroxylation of imipramine or desipramine and the mephenytoin S/R. These findings confirm those of an earlier panel study showing that the demethylation of imipramine and 2-OH-imipramine cosegregates in part with the mephenytoin oxidation polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Desipramine / blood
  • Desipramine / metabolism
  • Female
  • Humans
  • Hydroxylation
  • Imipramine / blood
  • Imipramine / metabolism*
  • Male
  • Mephenytoin / blood
  • Mephenytoin / metabolism*
  • Oxidation-Reduction
  • Polymorphism, Genetic
  • Sparteine / metabolism

Substances

  • Sparteine
  • Imipramine
  • Mephenytoin
  • Desipramine