Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers.

Objective: The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal gel, which served as the regulatory reference product; and oral diazepam, a product with decades of clinical use. Tolerability of diazepam nasal spray was also assessed.

Evaluation of Pharmacokinetics and Dose Proportionality of Diazepam After Intranasal Administration of NRL-1 to Healthy Volunteers.

NRL-1 is a novel intranasal formulation of diazepam that is being evaluated as rescue medication in patients with epilepsy who experience bouts of increased seizure activity despite stable regimens of antiepileptic drugs. This phase 1, open-label, randomized, crossover study in healthy adult volunteers consisted of 3 single-dose periods (5, 10, and 20 mg) followed by a 2-dose period (2 × 10 mg) with a minimum 28-day washout between treatments. Blood samples were taken at prespecified time points after intranasal dosing, and bioanalytic analysis of diazepam and nordiazepam was conducted using a validated liquid chromatography-tandem mass spectrometry method.