Effect of age on levels of diazepam in plasma and brain of rats

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Abstract
The pharmacokinetics and distribution in brain and cerebellum of diazepam after a single dose were studied in middle aged (6 months) and old (18 months) rats. Following the single intravenous bolus of 5 mg/kg diazepam was eliminated more slowly in old rats (T 1/2(β)=3.1h) than in middle aged rats (1.4 h). This was due to an increase in the apparent volume of distribution Vdβ from 11.0 l/kg (control rats) to 29.5l/kg. Concentrations of diazepam in brain and cerebellum were in the same range (0.5–1.1 ng/mg) in both groups after this dose. We conclude that the distribution of diazepam is age-dependent which might be due to an altered body composition.