Diazepam autoinjector intramuscular delivery system versus diazepam rectal gel: A pharmacokinetic comparison

SummaryRectal administration of diazepam (DZ) has been used effectively in patients with epilepsy who experience acute repetitive seizures, but rectal gel may be difficult to administer during a seizure and is subject to variable drug absorption. An intramuscular (IM) autoinjector DZ formulation may offer a practical alternative to rectal DZ. This single-center, open-label, 3-treatment, 3-period crossover study compared the pharmacokinetic and safety profiles of 10 mg DZ administered rectally in 24 healthy, fasted and fed subjects versus IM autoinjector delivery in fasted subjects. Blood samples were collected at baseline and for up to 24 h postdose and plasma DZ concentrations were determined by liquid chromatography and tandem mass spectrometry. There were no significant differences between plasma concentrations for rectal administration of DZ in fasted and fed subjects at any time point. Intramuscular DZ administration resulted in more rapid and less variable drug absorption than rectal delivery. At 30 min postdose and at all subsequent evaluations, IM administration resulted in significantly higher areas under the curve versus rectal administration in fasted subjects (p < 0.05). This significant difference was sustained throughout the remainder of the 24-h study period (p < 0.05). All reported adverse events were considered mild, and none required treatment.