Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

British Journal of Anaesthesia
S BjörkmanJ Idvall

Abstract

The aim of this study was to determine the bioavailability and absorption kinetics of midazolam given as an intranasal (i.n.) spray. In addition, plasma concentrations of the active metabolite, 1-hydroxymidazolam, were measured to give an indication of enteral absorption. An i.v. and i.n. midazolam dose were given in a crossover study to 14 adult surgical patients. Individual uptake profiles of i.n. midazolam were estimated by numerical deconvolution. After an i.n. dose of 0.15 mg kg-1, maximum arterial plasma concentrations were 192 (SD 48) micrograms litre-1 at 14 (2) min. Uptake of midazolam was rapid and bioavailability was 83 (15)%. Formation of the 1-hydroxy metabolite after i.n. administration did not exceed that after the i.v. dose. This demonstrates that under optimal conditions absorption of midazolam via the nasal mucosa was virtually complete. In this case little midazolam was swallowed and subjected to first-pass metabolism in the liver and therefore pharmacologically important amounts of active metabolite were not produced. Routinely administering i.n. midazolam under the assumption that the bioavailability is approximately 50% (as reported previously in the literature) may lead to overdosing in some patients.

Citations

Nov 10, 2006·European Radiology·Frank T C TschirchDominik Weishaupt
Apr 8, 2010·Pharmaceutical Research·Yin Cheong Wong, Zhong Zuo
Feb 13, 2001·International Journal of Pharmaceutics·T LoftssonE Stefánsson
Oct 24, 2002·British Journal of Clinical Pharmacology·M PeckingP Dostert
Mar 3, 2001·The Journal of Burn Care & Rehabilitation·S L HansenC N Paul
Mar 27, 2001·AJR. American Journal of Roentgenology·J HollenhorstS Piepenbrock
Apr 9, 2013·Pharmacological Reports : PR·Agnieszka BienertEdmund Grześkowiak
Jul 3, 2013·Revista española de anestesiología y reanimación·R Periñan BlancoM I de Molina Fernández
Feb 14, 2012·Advanced Drug Delivery Reviews·Gail D Anderson, Russell P Saneto
Jan 30, 2010·Clinical Therapeutics·Nicole M L Veldhorst-JanssenMarco A E Marcus
Feb 24, 2009·Epilepsy Research·Vijay D IvaturiJames C Cloyd
Jul 16, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Ivan Mario BraunMarcio Bernik
May 4, 2007·International Journal of Pharmaceutics·Henry R CostantinoSteven C Quay
Aug 14, 2010·Paediatric Anaesthesia·Brian J Anderson, Peter Larsson
Jun 23, 2010·British Journal of Clinical Pharmacology·Manuel HaschkeChristian Surber
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Yusuke OtaHideyuki Saito
Jan 24, 2007·Anesthesia and Analgesia·Matthias KarstMatthias Fink
Jul 25, 2006·Anesthesia and Analgesia·Daniel P WermelingAnita C Rudy
Apr 1, 2012·Anesthesiology and Pain Medicine·Ravi K VermaSurendra Gupta
May 18, 2012·The New England Journal of Medicine·Sven AsmussenMarc O Maybauer
Oct 22, 2016·British Journal of Clinical Pharmacology·Eva GermovsekJoseph F Standing
Jan 26, 2021·Drug Delivery and Translational Research·Lea-Adriana KellerAndreas Popp
Apr 14, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Iwona Zaporowska-StachowiakMaciej Sopata

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