Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis

Y. Sato, S. Shibanoki, M. Sugahara, K. Ishikawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The feasibibity 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. 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 μl 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. The intracerebral half life (t(1/2)) of Imip was 2.4 ± 0.3 h with Imip alone. Premedication with SKF-525A, an inhibitor of drug-metabolizing enzymes, significantly prolonged the t(1/2) 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. 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.

Original languageEnglish
Pages (from-to)625-629
Number of pages5
JournalBritish Journal of Pharmacology
Volume112
Issue number2
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Imipramine
Microdialysis
Pharmacokinetics
Desipramine
Brain
Proadifen
Aminopyrine
Premedication
Dialysis Solutions
Half-Life
Wistar Rats
Dialysis
High Pressure Liquid Chromatography

Keywords

  • Brain microdialysis
  • High-performance liquid chromatography with electrochemical detection
  • Imipramine
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis. / Sato, Y.; Shibanoki, S.; Sugahara, M.; Ishikawa, K.

In: British Journal of Pharmacology, Vol. 112, No. 2, 1994, p. 625-629.

Research output: Contribution to journalArticle

Sato, Y, Shibanoki, S, Sugahara, M & Ishikawa, K 1994, 'Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis', British Journal of Pharmacology, vol. 112, no. 2, pp. 625-629.
Sato, Y. ; Shibanoki, S. ; Sugahara, M. ; Ishikawa, K. / Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis. In: British Journal of Pharmacology. 1994 ; Vol. 112, No. 2. pp. 625-629.
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