摘要：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 Emax model. The pharmacodynamic paramenters from these models were not altered in renal dysfunction. In vitro binding studies for γ-aminobutyric acid (GABA)-benzodiazepine receptor complx, the oxazepam-induced effect was not potentiated by the plasma dialysate form renal dysfunction rats. Thus, it was suggested that the brain sensitibity to benzodiazepines was not altered in renal insufficiency.
