Intranasal Midazolam: Pharmacokinetics and Pharmacodynamics Assessed by Quantitative EEG in Healthy Volunteers

Clinical Pharmacology & TherapeuticsVolume 91, Issue 5 p. 856-862 Articles Intranasal Midazolam: Pharmacokinetics and Pharmacodynamics Assessed by Quantitative EEG in Healthy Volunteers M Hardmeier, M Hardmeier Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorR Zimmermann, R Zimmermann Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Rüegg, S Rüegg Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Pflüger, M Pflüger Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, Switzerland Department of Psychiatry, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Deuster, S Deuster University Hospital Pharmacy, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorK Suter, K Suter University Hospital Pharmacy, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Donzelli, M Donzelli Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorJ Drewe, J Drewe Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Krähenbühl, S Krähenbühl Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorP Fuhr, P Fuhr Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Haschke, Corresponding Author M Haschke mhaschke@uhbs.ch Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this author M Hardmeier, M Hardmeier Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorR Zimmermann, R Zimmermann Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Rüegg, S Rüegg Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Pflüger, M Pflüger Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, Switzerland Department of Psychiatry, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Deuster, S Deuster University Hospital Pharmacy, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorK Suter, K Suter University Hospital Pharmacy, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Donzelli, M Donzelli Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorJ Drewe, J Drewe Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorS Krähenbühl, S Krähenbühl Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorP Fuhr, P Fuhr Department of Neurology, Division of Clinical Neurophysiology, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this authorM Haschke, Corresponding Author M Haschke mhaschke@uhbs.ch Division of Clinical Pharmacology and Toxicology and Department of Biomedicine, University Hospital Basel, Basel, SwitzerlandSearch for more papers by this author First published: 28 March 2012 https://doi.org/10.1038/clpt.2011.316Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat 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 (Emax) 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. Clinical Pharmacology & Therapeutics (2012); 91 5, 856–862. doi:10.1038/clpt.2011.316 Citing Literature Volume91, Issue5Off-Label PrescribingMay 2012Pages 856-862 RelatedInformation