RESUMO
An open, randomized, cross-over study involving 24 healthy volunteers, shows that a novel formulation of temazepam (temazepam Gelthix, TG) in soft gelatin capsules designed to resist i.v. abuse has a similar pharmacokinetic (P-K) profile to that of a liquid-filled, reference formulation (TL) when administered as a single oral dose of 20 mg. The relative bioavailability of the two formulations assessed in terms of the area under the time versus plasma concentration profile (AUC), although statistically different (P less than 0.05), is well within the acceptable 80-120% limits for bioequivalence. Although the mean Cmax for TG (616.6 ng/ml) is lower than for TL (707.9 ng/ml) and the median time to reach Cmax (Tmax) is 40 min (TG) vs. 30 min (TL), there is no significant difference between TG and TL either in their absorption constant (Ka) (0.123 vs. 0.138 min-1 respectively) or their distribution (a) (29.5 vs. 32.4 min) and elimination (beta) (6.3 vs. 6.6 h) half-lives (t1/2). Thus the essential P-K characteristics for the use of temazepam as a hypnotic and premedicant, specifically a rapid rise followed by a prompt fall in blood levels, are conserved by the Gelthix formulation.
