Food interrupts absorption of diazepam nasal spray

Food appears to affect the pharmacokinetics of diazepam dosed via nasal spray, with absorption being markedly decreased and delayed, according to an open-label crossover study.

Researchers enrolled 24 healthy adults to examine the potential effects of food on the pharmacokinetics of diazepam nasal spray. Each participant received equal doses after two conditions: after an overnight fast and after a standardized high-fat, high-calorie breakfast, with a washout period of at least 21 days between treatments.

Of the participants, 20 (mean age 38.0 years, 75 percent men) completed the study and were included in the pharmacokinetic analysis. Their mean body mass index (BMI) was 26.3 kg/m². In terms of racial identities, 45 percent were Black/African American, 35 percent were White, 15 percent were multiracial, and 5 percent were Native Hawaiian or Other Pacific Islander.

Under high-fat, high-calorie breakfast conditions, the mean maximum plasma diazepam concentration dropped by 48 percent (p<0.0001) and the overall diazepam exposure within the first 4 hours decreased by 57 percent (p<0.0001) as compared with fasted conditions.

Moreover, the time to maximum plasma concentration was shorter by 2 hours in the fasted state than in the fed state (2.0 vs 4.0 hours; p<0.0001). At 2 hours after dosing, diazepam concentrations were ≥150 ng/mL in all participants when fasted and in only 30 percent when fed.

Finally, adverse events occurred more frequently in the fasted state than in the fed state (83.3 percent vs 54.5 percent; p=0.0340).