No abstract

Eleven healthy volunteers received a single intravenous dose of diazepam (0.15 mg/kg), midazolam (0.1 mg/kg), and placebo by 1-minute infusion in a double-blind, three-way crossover study. Plasma concentrations were measured during 24 hours after dosage, and the electroencephalographic (EEG) power spectrum was simultaneously computed by fast-Fourier transform to determine the percentage of total EEG amplitude occurring in the 13 to 30 Hz range. Both diazepam and midazolam had large volumes of distribution (1.2 and 2.3 L/kg, respectively), but diazepam's half-life was considerably longer (33 versus 2.8 hours) and its metabolic clearance lower (0.5 versus 11.0 ml/min kg) than those of midazolam. EEG changes were maximal at the end of the diazepam infusion and 5 to 10 minutes after midazolam infusion. Percent 13 to 30 Hz activity remained significantly above baseline until 5 hours for diazepam but only until 2 hours for midazolam. For both drugs, EEG effects were indistinguishable from baseline by 6 to 8 hours, suggesting that distribution contributes importantly to terminating pharmacodynamic action. The relationship of EEG change to plasma drug concentration indicated an apparent EC50 value of 269 ng/ml for diazepam as opposed to 35 ng/ml for midazolam. However, Emax values were similar for both drugs (+19.4% and +21.3%, respectively).

No abstract

Three benzodiazepine derivatives are currently indicated specifically for the treatment of insomnia in the United States. Flurazepam is biotransformed to at least two rapidly appearing and rapidly eliminated intermediate metabolites which probably contribute to sleep induction. The final metabolite, desalkylflurazepam, appears slowly, but has a long half-life ranging from 40 to 150 h. This metabolite accumulates extensively during multiple dosage. Temazepam is a slowly absorbed drug and has an intermediate half-life in the range of 10–20 h. Triazolam has an intermediate absorption rate, but is rapidly eliminated (half-life 1.5–5 h) making it essentially non-accumulating. Understanding of the pharmacokinetics of benzodiazepine hypnotics can contribute to understanding of their clinical properties.