Article date: November 2001
By: Karsten Lindhardt, Sveinbjörn Gizurarson, Sigurjón B. Stefánsson, David R. Òlafsson, Erik Bechgaard, in Volume 52, Issue 5, pages 521-527
Aims To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose‐effect relationships for diazepam administered nasally.
Methods The study had a cross‐over design with eight healthy volunteers (one 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 dose of diazepam. Changes in N100, P200 and P300 brain event‐related potentials (ERP) elicited by auditory stimulation and electroencephalographic β‐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 bioavailabilities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 58] and 42% [22, 62], respectively.
Conclusion The present study indicates that it is possible to deliver a clinically effective nasal dose of diazepam for the acute treatment of epilepsy, using PEG300 as a solubilizer.
DOI: 10.1046/j.0306-5251.2001.01486.x
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