Acute pharmacokinetic and pharmacodynamic comparison of two different formulations of temazepam

Twelve healthy subjects ingested temazepam 20 mg in two different formulations (soft gelatine capsule or uncoated tablet) and matched placebo at one-week intervals in double-blind and cross-over conditions. Venous blood was sampled before the drug intake and 0.5, 1, 2, 3, 8, 12, and 24 hours after it, and plasma temazepam concentrations were assayed by gas chromatography. Psychomotor performance was measured objectively (digit symbol substitution, letter cancellation, Maddox wing) and subjectively (visual analogue scales) before the drug intake and 1, 2, and 3 hours after it. Peak concentrations of plasma temazepam were reached at about one hour, and they were higher after the capsule than after the tablet (mean values 750 vs. 587 ng/ml), while the computed AUCs and elimination half-lives (6-22 hours) proved to be similar after either formulation. Impaired performance was measured in objective tests over the first three hours, the capsule being somewhat more effective than the tablet. Self-assessments indicating subjective sedation returned to the placebo level within 3 hours after the capsule but not after the tablet. This rapid subjective recovery after the capsule might result from an acute tolerance developed after the high peak, and it tallies with the lack of residual sedation previously reported in trials with temazepam 20 mg given in soft gelatine capsules.