Absorption of diazepam and lorazepam following intranasal administration

Abstract

The absorption characteristics of diazepam and lorazepam following intranasal administration were determined in order to assess the suitability of this approach for the treatment of status epilepticus in children. Due to the limited aqueous solubility of these drugs, a series of non-ionic surfactants were evaluated for drug solubility and nasal irritation. Cremophor EL (Blagden, U.K.) was selected as the least irritating. The diazepam and lorazepam studies were carried out in 2 and 4 healthy adults, respectively, in cross-over fashion. Diazepam was found to be 84% and 72% absorbed in the two subjects, peak concentration following nasal administration was observed at approximately 1 h and was approximately 27% of that following i.v. administration Lorazepam bioavailability ranged from 35% to 63%, peak time from 0.5 to 4 h, and peak concentration from 33% to 94% that following i.v. administration (even though the i.v. dose of lorazepam was 1 2 the intranasal dose). Although both drugs are absorbed following intranasal application, this route of administration would appear to have limited potential for the acute treatment of seizures.