Is temazepam an accumulating hypnotic?

Ten healthy volunteers aged 22 to 30 years received a single 20-mg oral dose of temazepam. Serum temazepam concentrations were measured by gas chromatography at multiple times during the next 48 hours. Mean kinetic variables were: volume of distribution, 1.45 liter/kg; elimination half-life, 8.6 hours; total clearance, 2.33 ml/min/kg. The subjects then received 20 mg temazepam once daily for seven consecutive days. Serum concentrations were measured just prior to each dose and at multiple time points after the last dose. Predose serum levels increased during the first three days of dosage, then increased no further. Mean values measured 24 hours after doses 1 through 6, respectively, were 33, 43, 55, 47, 53, and 51 ng/ml. Based on the area under the serum concentration curve after the last dose compared with that after the first dose, the mean accumulation ratio was 1.32, which was significantly greater than unity. The extent of accumulation was consistent with that predicted from the single-dose study. Postdosage washout half-life averaged 10.2 hours. Thus, temazepam has a pharmacokinetic profile of an intermediate half-life benzodiazepine that produces an intermediate degree of accumulation with multiple dosage.