Linked Life Data

8205373

Source:http://linkedlifedata.com/resource/pubmed/id/8205373

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-7-14
pubmed:abstractText
There is wide interindividual variation in steady-state plasma concentration of desipramine and other tricyclic antidepressants primarily due to differences in rates of hydroxylation. Several studies have shown that the rate of hydroxylation of desipramine is correlated with the rate of hydroxylation of the genetic probe drug, debrisoquine, which is controlled by monogenic inheritance. However, no population studies of the polymorphic metabolism of antidepressants have been reported. In this study, 59 patients with endogenous depression received a fixed dose of desipramine and the steady-state plasma concentration of desipramine and 2-hydroxydesipramine were determined by high-pressure chromatography. A new statistical approach based on optimizing the fit to a specific stochastic model was utilized to separate the mixture of the three genotypes: homozygous extensive (AA), heterozygous extensive (Aa) and poor (aa) metabolizers. The proportions of the genotypes are 0.43, 0.45 and 0.12, respectively. The gene frequency of the low-activity allele is 0.34 and that of the high-activity allele is 0.66. The means (SD) of the desipramine/2-hydroxydesipramine metabolic ratios of the three genotypes are 1.71 (0.44), 3.32 (1.68) and 23.32 (10.03). These data suggest that the heterozygous genotype has half the metabolic activity of the homozygous extensive metabolizer and that the poor metabolizer genotype has negligible metabolic activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0946-1965
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
126-30
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Pharmacogenetics of desipramine metabolism.
pubmed:affiliation
Department of Psychiatry, Loyola University Medical Center, Maywood, IL 60153.
pubmed:publicationType
Journal Article, Comparative Study