Hogan RE, et al. - By performing this phase 1, open-label, randomized, single-dose, three-treatment, three-period, six-sequence crossover study, researchers evaluated the bioavailability of diazepam following intranasal administration (diazepam nasal spray) in healthy volunteers (n = 48). Diazepam rectal gel and oral diazepam were included as comparative agents. They also evaluated the tolerability of diazepam nasal spray. Rapid onset of diazepam absorption was reported for all routes of delivery, with measurable levels of drug present by the first sample time point. Diazepam nasal spray and diazepam rectal gel had similar tmax (time to reach maximum plasma concentration), both were slower compared with oral diazepam in fasted individuals. The observed variability (as defined by % coefficient of variation of geometric mean) in peak plasma level and area under the curve0-∞ was the lowest with oral diazepam, followed by diazepam nasal spray, with diazepam rectal gel displaying the greatest variability. Mild treatment-emergent adverse events (TEAEs) were 131, moderate TEAEs were four, and no TEAEs were considered severe. Overall, predicable pharmacokinetics was displayed by diazepam nasal spray, and it affords a potentially new treatment approach to control bouts of increased seizure activity (cluster seizures, acute repetitive seizures).