Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy.

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Morinobu S, Tanaka T, Kawakatsu S, Totsuka S, Koyama E, Chiba K, Ishizaki T, Kubota T

Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy.

Psychiatry Clin Neurosci. 1997 Aug;51(4):253-7.

PubMed ID

9316174 [ View in PubMed

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Abstract

The relationship between the genetic polymorphism of S-mephenytoin 4'-hydroxylation catalyzed by CYP2C19 and the N-demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S-mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2-hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N-demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Imipramine	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate Inhibitor	Details