Authors: Heedoo Yoo Timo Iirola Sanna Vilo Tuula Manner Riku Aantaa Maria Lahtinen Mika Scheinin Klaus T Olkkola William J Jusko
Publish Date: 2015/08/02
Volume: 71, Issue: 10, Pages: 1197-1207
Abstract
Dexmedetomidine is an α2adrenoceptor agonist used for perioperative and intensive care sedation This study develops mechanismbased population pharmacokineticpharmacodynamic models for the cardiovascular and central nervous system CNS effects of intravenously IV and intranasally IN administered dexmedetomidine in healthy subjectsSingle doses of 84 μg of dexmedetomidine were given once IV and once IN to six healthy men Plasma dexmedetomidine concentrations were measured for 10 h along with plasma concentrations of norepinephrine NE and epinephrine E Blood pressure heart rate and CNS drug effects three visual analog scales and bispectral index were monitored to assess the pharmacological effects of dexmedetomidine PKPD modeling was performed for recently published data Eur J Clin Pharmacol 67 825 2011Pharmacokinetic profiles for both IV and IN doses of dexmedetomidine were well fitted using a twocompartment PK model Intranasal bioavailability was 82 Dexmedetomidine inhibited the release of NE and E to induce their decline in blood This decrease in NE was captured with an indirect response model The concentrations of the mediator NE served via a biophase/transduction step and nonlinear pharmacologic functions to produce reductions in blood pressure and heart rate while a direct effect model was used for the CNS effects
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