Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine |
| |
Authors: | K Brøsen L F Gram |
| |
Institution: | (1) Department of Clinical Pharmacology, Odense University, Odense C, Denmark |
| |
Abstract: | Summary 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. |
| |
Keywords: | imipramine desipramine quinidine sparteine oxidation cytochrome P450 isoforms genetic polymorphism drug interaction metabolic clearance |
本文献已被 SpringerLink 等数据库收录! |
|