Document Detail


Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis.
MedLine Citation:
PMID:  8075879     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The feasibility of the brain microdialysis method for direct measurement and pharmacokinetic study of imipramine (Imip) and its metabolite desipramine (DMI) was investigated in the rat brain. 2. A dialysis tube was inserted into the right striatum of male Wistar rats, which were administered i.p. with 12.5 mg kg-1 Imip. Thirty microliters dialysate was collected every 15 min, and the levels of Imip and DMI were measured by high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.d.). SKF-525A and aminopyrine were concomitantly administered in order to assess their respective effects on the pharmacokinetics of Imip and DMI in the brain. 3. The intracerebral half life (t1/2) of Imip was 2.4 +/- 0.3 h with Imip alone. Premedication with SKF-525A, an inhibitor of drug-metabolizing enzymes, significantly prolonged the t1/2 of Imip, while at the same time production of DMI from Imip was accordingly inhibited. Concomitant administration of aminopyrine did not induce any significant change in the concentrations of Imip, but significantly inhibited the concentrations of DMI through its competitive antagonism in the demethylation pathway. 4. The present results suggest that the brain microdialysis method reflects the intracerebral pharmacokinetics of Imip and DMI well and may be applicable to further pharmacokinetic investigations of psychotropic agents.
Authors:
Y Sato; S Shibanoki; M Sugahara; K Ishikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  112     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-10-05     Completed Date:  1994-10-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  625-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Nihon University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aminopyrine / pharmacology
Animals
Brain / drug effects,  metabolism*
Chromatography, High Pressure Liquid
Desipramine / analysis,  pharmacokinetics
Electrochemistry
Half-Life
Imipramine / pharmacokinetics*
Male
Microdialysis
Proadifen / pharmacology
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
302-33-0/Proadifen; 50-47-5/Desipramine; 50-49-7/Imipramine; 58-15-1/Aminopyrine
Comments/Corrections

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