Effect of sleep on quazepam kinetics.

The effect of sleep on quazepam kinetics was studied in 12 normal adult men. In a randomized two-way crossover design, each subject received one 15-mg quazepam tablet either at night just before sleep or in the morning after a night's sleep. Blood samples were drawn before and at specified times (to 120 hr) after dosing. To assure that blood collection did not interfere with sleep, blood was drawn by an indwelling catheter from a large arm vein. Plasma concentrations of quazepam and its two major plasma metabolites (which are also active) 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam) were determined by specific GLC methods. Kinetic analysis was by a two-compartment open model with first-order absorption/formation kinetics. Quazepam was rapidly absorbed with both administration times; absorption t 1/2 was 0.7 to 0.9 hr. Absorption lag time was slightly longer after the nighttime dose (1.0 and 0.6 hr). Maximum concentration and AUC of quazepam and 2-oxoquazepam and AUC of N-desalkyl-2-oxoquazepam were somewhat higher after nighttime dosing, most likely a result of decreased apparent volume of distribution of the central compartment after the nighttime dose (5.0 l/kg for nighttime dosing and 8.6 l/kg for morning dosing). The elimination t 1/2s of quazepam, 2-oxoquazepam, and N-desalkyl-2-oxoquazepam after the morning dose were 25, 28, and 79 hr, which did not differ from those values after the nighttime dose. In general, time of dosing had no appreciable effect on quazepam kinetics or those of its major active plasma metabolites. The small differences between the two dose times are not expected to have clinical significance.