Pharmacokinetics of amitriptyline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of amitriptyline

The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner a...

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Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 79; no. 4; p. 288
Main Authors Miyake, K, Fukuchi, H, Kitaura, T, Kimura, M, Sarai, K, Nakahara, T
Format Journal Article
LanguageEnglish
Published United States 01.04.1990
Subjects
Amitriptyline - administration & dosage
Amitriptyline - blood
Amitriptyline - pharmacokinetics
Animals
Brain - metabolism
Dealkylation
Injections, Intraperitoneal
Male
Nortriptyline - blood
Nortriptyline - metabolism
Rats
Rats, Inbred Strains
Solubility
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Summary:The concentrations of amitriptyline (AMT) and its demethylated metabolite nortriptyline (NRT) in the serum and in specific brain regions were determined periodically after acute or chronic administration of 20 mg/kg of AMT in rats. Both AMT and NRT declined from the serum in a biexponential manner and were eliminated monoexponentially from the brain regions, with no significant difference in elimination among the eight brain regions examined. In the brain, both AMT and NRT were unevenly distributed after chronic administration, whereas an even distribution was observed after acute administration. The AUCbrain:AUCserum ratio of AMT was higher than that of NRT, indicating greater transport of AMT into the brain regions. The AUCAMT value in the serum increased 1.6 times after chronic administration, whereas no significant changes were observed in the brain regions. The AUCNRT values increased 9.0 times in the serum and 6.8 times in the brain, with the increase in the serum being greater. These results suggest inhibited distribution of the drugs into the tissues, including the brain regions, and enhanced metabolism of AMT.
ISSN:0022-3549
DOI:10.1002/jps.2600790403