Bioavailability of intranasal vs. rectal diazepam.

Area of Science:

• Pharmacology
• Emergency Medicine
• Drug Delivery Systems

Background:

• Rectal diazepam (DZP) is used for out-of-hospital seizure emergencies but faces social objections, particularly in older children and adults.
• Previous intranasal DZP studies showed feasibility and comparable pharmacokinetics to rectal administration but poor tolerability.
• An unmet medical need exists for well-tolerated and effective out-of-hospital seizure emergency treatments.

Purpose of the Study:

• To compare the tolerability and pharmacokinetics of two novel intranasal diazepam formulations against the standard rectal gel.
• To evaluate the potential of intranasal diazepam as a viable alternative to rectal administration for seizure emergencies.

Main Methods:

• A double-blind, four-period crossover study involving twelve healthy volunteers.
• Comparison of three intranasal diazepam treatments (Nas-A 10mg, Nas-B 10mg, Nas-B 13.4mg) with 10mg rectal diazepam gel.
• Assessment of plasma diazepam concentrations, time to maximum concentration (Tmax), maximum plasma concentration (Cmax), bioavailability, tolerability, and sedation via visual analog scales.

Main Results:

• Intranasal formulations demonstrated Cmax values comparable to rectal diazepam (151.3–181.8 ng/mL vs. 160.9 ng/mL).
• Median Tmax was 0.75 hours for all treatments, indicating rapid absorption.
• Intranasal formulations were well-tolerated, with relative bioavailability of 70-90% compared to rectal gel, though absorption was variable.

Conclusions:

• Development of well-tolerated intranasal diazepam formulations is feasible, approximating the absorption profile of rectal diazepam.
• Intranasal diazepam presents a promising alternative to rectal administration for seizure emergencies.
• Further formulation enhancement is necessary to improve the extent and consistency of intranasal diazepam absorption.