title: The N-demethylation of imipramine correlates with the oxidation of S-mephenytoin (S/R-ratio). A population study.
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.
authors: Department of Clinical Pharmacology, IMB, Odense University, Denmark.
authors: E
authors: E
authors: Skjelbo
authors: L F
authors: LF
authors: Gram
authors: K
authors: K
authors: Brøsen
mesh_terms: D000293:Adolescent; D000328:Adult; D003891:Desipramine / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007099:Imipramine / Q000097:blood / Q000378:metabolism*; D008297:Male; D008617:Mephenytoin / Q000097:blood / Q000378:metabolism*; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D013034:Sparteine / Q000378:metabolism
chemical_list: D013034:Sparteine; D007099:Imipramine; D008617:Mephenytoin; D003891:Desipramine