Bioavailability and tolerability of intranasal diazepam in healthy adult volunteers

Vijay D. Ivaturi, Jennifer R. Riss, Robert L. Kriel, Ronald A Siegel, James C Cloyd

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Intranasal therapy has been proposed as an alternative for the management of seizure emergencies. The bioavailability, dose proportionality and tolerability of a supersaturated intranasal formulation of diazepam (DZP) solubilized in a glycofurol-water cosolvent system was investigated. Eight healthy volunteers were randomized into a single-blind, three-way crossover study to compare 5 and 10 mg intranasal DZP doses of the investigational formulation with a 5 mg dose of a DZP solution (DZP injectable, 5 mg/mL) administered intravenously. Treatments were separated by a two-week washout period. Plasma samples for DZP analysis were collected pre-dose and at regular intervals up to 48 h post-dose and assayed by HPLC. Visual analog scales (VAS) were used to assess tolerability (1-tolerable; 10-extremely intolerable) and pain (1-no pain; 4-extreme pain) at predefined time points. Following the 5 and 10 mg doses, the median tmax were 20 and 30 min and the mean Cmax were 134.3 ± 62 and 247.6 ± 61 ng/mL. Estimated bioavailability was 75% for both doses. Pain scores of 2 and 2.3 were observed following the 5 and 10 mg doses; tolerability scores were 4.4 and 4.7. Pain and tolerability scores returned to baseline within 10 h. Our formulation provided reasonable bioavailability, but was not well tolerated.

Original languageEnglish (US)
Pages (from-to)120-126
Number of pages7
JournalEpilepsy Research
Issue number2-3
StatePublished - Apr 2009

Bibliographical note

Funding Information:
We would like to thank Usha Mishra for her help with the DZP assay. We would also like to acknowledge Parents Against Childhood Epilepsy (PACE), the Epilepsy Foundation and Valeant Pharmaceuticals for funding this project.

Copyright 2009 Elsevier B.V., All rights reserved.


  • Diazepam
  • Glycofurol
  • Intranasal therapy
  • Out-of-hospital
  • Seizure emergencies


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