Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans

2.50
Hdl Handle:
http://hdl.handle.net/2336/82955
Title:
Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans
Authors:
Gudmundsdottir, H; Sigurjonsdottir, J F; Masson, M; Fjalldal, O; Stefansson, E; Loftsson, T
Citation:
Pharmazie. 2001, 56(12):963-6
Issue Date:
1-Dec-2001
Abstract:
Intranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.govi.de/pharmazie.htm

Full metadata record

DC FieldValue Language
dc.contributor.authorGudmundsdottir, Hen
dc.contributor.authorSigurjonsdottir, J Fen
dc.contributor.authorMasson, Men
dc.contributor.authorFjalldal, Oen
dc.contributor.authorStefansson, Een
dc.contributor.authorLoftsson, Ten
dc.date.accessioned2009-09-29T11:33:11Z-
dc.date.available2009-09-29T11:33:11Z-
dc.date.issued2001-12-01-
dc.date.submitted2009-09-29-
dc.identifier.citationPharmazie. 2001, 56(12):963-6en
dc.identifier.issn0031-7144-
dc.identifier.pmid11802661-
dc.identifier.urihttp://hdl.handle.net/2336/82955-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractIntranasal administration of midazolam has been of particular interest because of the rapid and reliable onset of action, predictable effects, and avoidance of injections. The available intravenous formulation (Dormicum i.v. solution from Hoffmann-La Roche) is however less than optimal for intranasal administration due to low midazolam concentration and acidity of the formulation (pH 3.0-3.3). In this study midazolam was formulated in aqueous sulfobutylether-beta-cyclodextrin buffer solution. The nasal spray was tested in 12 healthy volunteers and compared to intravenous midazolam in an open crossover trial. Clinical sedation effects, irritation, and serum drug levels were monitored. The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation). The peak serum concentration from nasal application, 42 +/- 11 ng ml-1, was reached within 10-15 min following administration and clinical sedative effects were observed within 5 to 10 min and lasted for about 40 min. Intravenous administration gave clinical sedative effects within 3 to 4 min, which lasted for about 35 minutes. Mild to moderate, transient irritation of nasal and pharyngeal mucosa was reported. The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed.en
dc.language.isoenen
dc.publisherGovi-Verlag Pharmazautischer Verlagen
dc.relation.urlhttp://www.govi.de/pharmazie.htmen
dc.subject.meshAdministration, Intranasalen
dc.subject.meshAdulten
dc.subject.meshAerosolsen
dc.subject.meshBiological Availabilityen
dc.subject.meshCyclodextrinsen
dc.subject.meshExcipientsen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshHypnotics and Sedativesen
dc.subject.meshIndicators and Reagentsen
dc.subject.meshInjections, Intravenousen
dc.subject.meshIrritantsen
dc.subject.meshMaleen
dc.subject.meshMicroscopy, Electron, Scanningen
dc.subject.meshMidazolamen
dc.titleIntranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humansen
dc.typeArticleen
dc.contributor.departmentDepartment of Ophthalmology, National University Hospital, University of Iceland, Reykjavik, Iceland.en
dc.identifier.journalPharmazieen

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