Abstract
The relationship between the quantitative EEG variables and plasma levels after the administration of diazepam (DZ) or N-desmethyldiazepam (synthesized NDDZ) was evaluated by simultaneously measuring the power spectra for EEG with two biological markers and plasma concentrations. After a single DZ administration, the EEG change corresponding to sedation appeared rapidly and showed a short duration. A close relationship was found between these effects and changes in the DZ plasma concentrations. DZ and synthesized NDDZ had the same pharmacodynamic characteristics, but the main metabolic product of DZ (metabolite NDDZ) showed a different pharmacokinetic profile. A multiple administration of DZ or synthesized NDDZ caused some reduction in sedation at the steady-state. These results led to the conclusions that a single administration of DZ causes sedation of a short duration, and the main metabolic product of DZ (metabolite NDDZ) does not seem to contribute to sedation. In addition, the reduction in the pharmacological effect after continuous treatment with DZ depends not on autoinduction or interference, but on acute tolerance or adaptation.
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