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

Aims To evaluate the electroencephalographic (EEG) effects, blood concentra tions, vehicle irritation and dose-effect relationships for diazepam admini stered nasally. Methods The study had a cross-over design with eight healthy volunteers (on e drop out). It consisted of four legs with four different administrations: intranasal (i.n.) placebo, 4 mg diazepam i.n., 7 mg diazepam i.n. and 5 mg intravenous (i.v.) diazepam. Polyethylene glycol 300 (PEG300) was used as a vehicle in the nasal formulations to solubilize a clinically relevant dos e of diazepam. Changes in N100, P200 and P300 brain event-related potential s (ERP) elicited by auditory stimulation and electroencephalographic beta - activity were used to assess effects on neurological activity. Results The mean [95% confidence intervals] differences between before and after drug administration values of P300-N100 amplitude differences were -0 .9 [ -6.5, 4.7] -6.4 [-10.1, -2,7], -8.6 [-11.4, -5.8] and -9.6 [-12.1, -7. 1] for placebo, 4 mg i.n., 7 mg i.n. and 5 mg i.v. diazepam, respectively, indicating statistically significant drug induced effects. The bioavailabil ities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 5 8] and 42% [22, 62], respectively. Conclusion The present study indicates that it is possible to deliver a cli nically effective nasal dose of diazepam for the acute treatment of epileps y, using PEG300 as a solubilizer.