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

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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.

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  1. Department of Clinical Pharmacology, Odense University, Odense C, Denmark

    K. Brøsen & L. F. Gram

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  1. K. Brøsen
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  2. L. F. Gram
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Brøsen, K., Gram, L.F. Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine. Eur J Clin Pharmacol 37, 155–160 (1989). https://doi.org/10.1007/BF00558224

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  • DOI: https://doi.org/10.1007/BF00558224

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