Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine.
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.
Brøsen
K
K
Department of Clinical Pharmacology, Odense University, Denmark.
Gram
L F
LF
D000328:Adult; D003640:Dealkylation; D003891:Desipramine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D007099:Imipramine / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D010641:Phenotype; D011802:Quinidine / Q000494:pharmacology*; D013034:Sparteine / Q000378:metabolism
D013034:Sparteine; D011802:Quinidine; D007099:Imipramine; D003891:Desipramine; C028653:2-hydroxydesipramine