Pharmacodynamic correlates of modified absorption: studies with lormetazepam

The bioavailability, pharmacokinetics, and effects on performance of lormetazepam (1 mg) have been compared using soft gelatin capsule and tablet formulations. Lormetazepam was more rapidly absorbed from the soft gelatin capsule (tmax = 1.0 +/- 0.2 h) than from the tablet (tmax = 2.4 +/- 0.4 h), and the plasma concentration-time curve for the capsule was shifted to the left. Bioavailability and elimination kinetics did not differ between the formulations. The number of substitutions in the digit symbol test was reduced between 0.5 and 1.5 h for both formulations (P less than 0.001), but the degree of impairment at 0.5 h was greater after the capsule than after the tablet (P less than 0.01). Visuo-motor co-ordination was impaired from 0.5 to 1.5 h after the tablet and the capsule (P less than 0.01), and extended to 5.5 h after the tablet (P less than 0.05). These observations reflect the differences in the plasma concentration-time curves.