Single dose pharmacokinetics and pharmacodynamics of oxazepam in normal and renal dysfunction rats

Kalpana Srivastava, Tomomi Hatanaka, Tetsuya Aiba, Kazunori Katayama, Tamotsu Koizumi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The purpose of this work was to investigate the disposition characteristics and pharmacodynamics of a benzodiazepine, oxazepam, in renal dysfunction rats. For the in vivo experiment, normal and renal dysfunction rats were given 40 mg/kg of oxazepam as the bolus dose. A quantitative electroencephalographic (EEG) method was used as the surrogate measure of the pharmacological response. The oxazepam concentration in plasma and cerebrospinal fluid (CSF) was assayed by the HPLC method. The steady-state volume of distribution and clearance based on total and unbound plasma did not change in renal dysfunction rats. Amplitude changes in the EEG induced by oxazepam in normal and renal dysfunction rats were characterized by a log- concentration response model or sigmoidal E(max) model. The pharmacodynamic parameters from these models were not altered in renal dysfunction. In in vitro binding studies for γ-aminobutyric acid (GABA)-benzodiazepine receptor complex, the oxazepam-induced effect was not potentiated by the plasma dialysate from renal dysfunction rats. Thus, it was suggested that the brain sensitivity to benzodiazepines was not altered in renal insufficiency.

Original languageEnglish
Pages (from-to)627-632
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume22
Issue number6
DOIs
Publication statusPublished - Jun 1999
Externally publishedYes

Keywords

  • Oxazepam
  • Pharmacodynamics
  • Pharmacokinetics
  • Rat
  • Renal dysfunction
  • γ- aminobutyric acid(A) (GABA(A)) receptor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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