Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

Abstract

A diazepam 10-mg autoinjector was evaluated in bioequivalence and dose proportionality studies; both involved 24 young, healthy subjects and used randomized, open-label, 2-treatment, 2-period crossover designs with a 3-week washout period between treatments. The bioequivalence study compared a single diazepam 10-mg autoinjector with a conventional needle and syringe containing 10 mg of diazepam injectable. The dose proportionality study compared the pharmacokinetics of a single diazepam 10-mg autoinjector with that of 2 diazepam 10-mg autoinjectors given simultaneously (20 mg). Injections were intramuscular in the midanterolateral thigh in both studies. The studies showed that the diazepam autoinjector produced consistent plasma diazepam levels, with a rapid onset of absorption. The diazepam 10-mg autoinjector given intramuscularly was bioequivalent to a conventional syringe containing diazepam 10 mg. A single (10-mg) autoinjector and 2 (20-mg) diazepam autoinjectors administered simultaneously produced plasma diazepam concentrations that were essentially dose proportional.

In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems

“…The initial precipitation observed with DZP reduced over time, possibly due to the precipitate being amorphous or a polymorph, which could readily redissolve. This supports reports of biphasic intramuscular absorption of DZP . Additionally, high inter‐individual variability was observed for absorption parameters ( C max and t max ) after intramuscular injection of DZP, resulting in clinical failure in some cases.…”

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

“…A Phase I study investigating bioequivalence and dose proportionality showed that DZP 10 mg auto-injection in the anterolateral thigh was bioequivalent to DZP injected with a conventional syringe [40]. In addition, this study also suggested that the site of injection is important because the gluteus or the deltoid muscles may lead to inconsistent absorption.…”

Quick treatment with the most appropriate benzodiazepine formulation is vital when treating acute repetitive seizures in the outpatient setting

“…Intramuscular diazepam administered by autoinjector as shown efficacy in the treatment of ARS [9,10] (Table 1) and appears to be rapidly absorbed [24,25]. Two studies in healthy volunteers demonstrated that intramuscular autoinjection was bioequivalent to intramuscular injection with a conventional syringe [24].…”

“…Two studies in healthy volunteers demonstrated that intramuscular autoinjection was bioequivalent to intramuscular injection with a conventional syringe [24]. Other studies found that diazepam administered intramuscularly by autoinjector was absorbed more rapidly than rectal diazepam [25], with slightly higher bioavailability [26].…”