Intranasal Administration of Diazepam Aiming at the Treatment of Acute Seizures: Clinical Trials in Healthy Volunteers.

Intranasal Delivery of Two Benzodiazepines, Midazolam and Diazepam, by a Microemulsion System

“…As shown in Table 2, the absolute bioavailability of DZP after IN administration using this formulation was 33.45% ± 12.36% and the t max was 18.33 ± 23.09 min, which was twice longer than the t max obtained after MDZ administration (9.25 ± 6.75 min). The t max values obtained in this study for diazepam is in agreement with Gizurarson, et al [13], who achieved peak levels after 18 ± 11 min in healthy humans. The difference between t max values of DZP and Table 1.…”

“…By the alternative route, diazepam should be easily administered by the surrounding people or caregivers and could dramatically improve the management of out-of-hospital seizures as well as the patient recovery. The intranasal administration of diazepam was evaluated in several studies, in which supersaturated formulations were used with solvents such as a glycofurol/water mixture [7,12], glycofurol/polyethylene glycol 200 [13,14], propylene glycol/ethanol [15], and polyethylene glycol 300 [16]. Human studies [7,12], which were conducted on human volunteers reported that subjects rated nasal diazepam as causing considerable pain immediately following administration.…”

Benzodiazepines for prolonged seizures

“…For diazepam, some pharmacokinetic data exist: after intranasal administration of diazepam to nine adult volunteers, a t max of 18 ± 11 min was observed with bioavailability of 50.4 ± 23.3%,37 but no trial appears to have been carried out in clinical practice.…”

Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers

“…In rabbits, a peak serum concentration is obtained about 5 min after the administration [1]. Diazepam has poor water solubility, but polyethylene glycol 300 (PEG300), a vehicle causing relatively little local irritation, has been found to solubilize an expected clinically relevant dose (4±10 mg) of diazepam in the limited volume necessary for nasal administration [2].…”

“…In an earlier clinical study a nasal dose of 2 mg diazepam was administered by use of PEG300 as the solubilizing vehicle [2]. Within 30 min the nasal bioavailability was found to be about 37%.…”