December 9, 2022

A Randomized, Open-Label, Two-Treatment Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of Diazepam Nasal Spray (Valtoco ®) in Healthy Adult Subjects

Abstract found on Wiley Online Library

Objective: The pharmacokinetics of oral diazepam are affected by food, but food effect studies have not been conducted for diazepam nasal spray because it is believed that most absorption occurs via the nasal mucosa. However, gastrointestinal side effects reported with nasal diazepam suggest that at least a portion of the drug may be absorbed enterally and thus subject to food effects. The objective of this study was to evaluate the possible effects of food on the pharmacokinetics of diazepam nasal spray in healthy adults.

Methods: This randomized, open-label crossover study compared equal doses of diazepam nasal spray after an overnight fast and after a standardized high-fat, high-calorie breakfast. Each subject served as their own control, and there was a washout period of at least 21?days between treatments.

Results: Twenty-four healthy adults enrolled in this study. Two subjects withdrew consent, and two subjects had pre-dose diazepam concentrations that exceeded the protocol-defined minimum after the washout period and were excluded from the final analysis population of 20 subjects. Under fed conditions, the mean maximum plasma diazepam concentration was decreased by 48% (P <0.0001) and the overall diazepam exposure during the first four hours was reduced by 57% (P <0.0001) compared with fasted conditions. The time to maximum plasma concentration was 4.0 hours in the fed state compared with 2.0 hours in the fasted state (P <0.0001). At two hours post-dose, diazepam concentrations were ?150 ng/mL for 100% of subjects when fasted and 30% when fed. Significantly more subjects experienced adverse events when fasted (83.3%) than when fed (54.5%; P =?0.0340).

Significance: This study in healthy volunteers demonstrated that food significantly decreases and delays the absorption of diazepam dosed via nasal spray. Patients using diazepam nasal spray after eating may obtain diazepam concentrations that are below those needed for seizure control.