Document Detail

Bioavailability of Intranasal vs. Rectal Diazepam.
MedLine Citation:
PMID:  22981338     Owner:  NLM     Status:  Publisher    
There remains an unmet medical need in the out-of-hospital management of seizure emergencies because older children and adults often refuse treatment with diazepam rectal gel due to social objections. We have previously reported that intranasal diazepam (DZP) administration is feasible, with maximum plasma concentrations (C(max)) and time to maximum concentration (T(max)) that are comparable to rectal DZP; but tolerability was poor. In the present study, the tolerability and pharmacokinetics of two investigational nasal formulations were compared with DZP rectal gel. Twelve healthy volunteers were enrolled into an active-control, double-blind, four-period, crossover pharmacokinetic and tolerability study. Three intranasal treatments (Nas-A 10mg, Nas-B 10mg and Nas-B 13.4mg) were compared to a 10mg dose of the rectal gel. A single dose of each formulation was administered followed by at least a 14day washout period. Blood samples for plasma DZP concentration-time characterization were collected pre-dose and at regular intervals to 240h post-dose. Tolerability and sedation were assessed using visual analog scales. Mean DZP C(max) (±SD) was 181.8±84.16, 151.3±108.1 and 180.7±82.1ng/mL for Nas-A 10mg, Nas-B 10 and Nas-B 13.4mg respectively; in comparison the C(max) for the rectal gel was 160.9±109.4ng/mL. Median T(max) was 0.75h for all treatments. Both intranasal formulations were well tolerated and exhibited relatively rapid, but variable, absorption with bioavailability of 70-90% relative to DZP rectal gel. This study shows that the development of a well-tolerated nasal formulation is possible and that the rate and extent of absorption approximates that of DZP rectal gel. We conclude that intranasal DZP offers a viable alternative to rectal administration, but enhancement of formulations is needed to improve the extent and consistency of absorption.
Vijay Ivaturi; Robert Kriel; Richard Brundage; Gordon Loewen; Hank Mansbach; James Cloyd
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-12
Journal Detail:
Title:  Epilepsy research     Volume:  -     ISSN:  1872-6844     ISO Abbreviation:  Epilepsy Res.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8703089     Medline TA:  Epilepsy Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Center for Orphan Drug Research, United States; Department of Experimental and Clinical Pharmacology, University of Minnesota, United States. Electronic address:
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