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Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers

Hardmeier, M. and Zimmermann, R. and Rüegg, S. and Pflüger, M. and Deuster, S. and Suter, K. and Donzelli, M. and Drewe, J. and Krähenbühl, S. and Fuhr, P. and Haschke, M.. (2012) Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers. Clinical Pharmacology & Therapeutics, 91 (5). pp. 856-862.

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Official URL: http://edoc.unibas.ch/dok/A6083675

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Abstract

The pharmacokinetics and pharmacodynamics of a highly concentrated cyclodextrin-based intranasal (i.n.) midazolam formulation containing the absorption-enhancer chitosan were studied in 12 healthy volunteers and compared with intravenous (i.v.) midazolam. The pharmacodynamic (PD) effects were assessed using quantitative electroencephalography (EEG). Maximal plasma concentrations of 63 and 110 ng/ml were reached at 8.4 and 7.6 min after 3 and 6 mg i.n. midazolam, respectively. After 5 mg i.v. and 6 and 3 mg i.n. midazolam, the times to onset of significant EEG effects in the β2 band (18-25 Hz) were 1.2, 5.5, and 6.9 min, respectively, and the times to loss of response to auditory stimuli were 3.0, 8.0, and 15.0 min, respectively. A sigmoid maximum-effect (E(max)) model indicated disequilibrium between plasma and effect-site concentrations, with equilibration half-lives of 2.1-4.8 min. The observed pharmacokinetic-PD (PK-PD) properties suggest that i.n. midazolam deserves to be evaluated as an easy and noninvasive method of administering a first benzodiazepine dose, e.g., in out-of-hospital emergency settings with no immediate i.v. access.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Pharmacology (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Pharmakologie (Krähenbühl)
UniBasel Contributors:Krähenbühl, Stephan and Zimmermann, Ronan and Hardmeier, Martin and Pflüger, Marlon and Deuster, Stefanie and Donzelli, Massimiliano and Drewe, Jürgen and Fuhr, Peter and Haschke, Manuel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:0009-9236
e-ISSN:1532-6535
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:19 Oct 2023 15:11
Deposited On:26 Apr 2013 06:59

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