Pharmacokinetics of imipramine are affected by age and sex in rats

Marlene A. Wilson, Edward J. Roy

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic treatment with the antidepressant imipramine (IMI) leads to accumulation of imipramine's major metaboite desmethylimipramine (DMI) in the brain. Juvenile, young and middle-aged female rats, as well as juvenile and young male rats were treated chronically with imipramine (14 days) and analyzed 24 hours later for levels of IMI and DMI in the hypothalamus-preoptic area (HPA) and serum. Older animals of both sexes showed higher levels of DMI than juvenile animals, in both the HPA and serum. Females also had higher DMI levels than males at comparable ages. Analysis of IMI and DMI levels at intervals after a single imipramine injection suggested that the initial metabolism of imipramine is slower in older animals and in females (compared to males). The results indicate that age and gender alter the initial metabolism of imipramine, leading to enhanced accumulation of metabolites during chronic treatment in older animals and in female rats, compared to younger rats and males, respectively.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalLife Sciences
Volume38
Issue number8
DOIs
StatePublished - Feb 24 1986

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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