title: Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine.
abstract: Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug's peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative. Dexmedetomidine is rapidly distributed and is mainly hepatically metabolized into inactive metabolites by glucuronidation and hydroxylation. A high inter-individual variability in dexmedetomidine pharmacokinetics has been described, especially in the intensive care unit population. In recent years, multiple pharmacokinetic non-compartmental analyses as well as population pharmacokinetic studies have been performed. Body size, hepatic impairment, and presumably plasma albumin and cardiac output have a significant impact on dexmedetomidine pharmacokinetics. Results regarding other covariates remain inconclusive and warrant further research. Although initially approved for intravenous use for up to 24 h in the adult intensive care unit population only, applications of dexmedetomidine in clinical practice have been widened over the past few years. Procedural sedation with dexmedetomidine was additionally approved by the US Food and Drug Administration in 2003 and dexmedetomidine has appeared useful in multiple off-label applications such as pediatric sedation, intranasal or buccal administration, and use as an adjuvant to local analgesia techniques.
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Maud A S
authors.initials: MAS
authors.lastname: Weerink
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. m.m.r.f.struys@umcg.nl.|Department of Anesthesia and Peri-operative Medicine, Ghent University, Ghent, Belgium. m.m.r.f.struys@umcg.nl.
authors.forename: Michel M R F
authors.initials: MMRF
authors.lastname: Struys
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Hannivoort
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Clemens R M
authors.initials: CRM
authors.lastname: Barends
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Absalom
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.|Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Colin
mesh_terms: D000278:Administration, Buccal; D000281:Administration, Intranasal; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000758:Anesthesia; D015992:Body Mass Index; D001919:Bradycardia / Q000139:chemically induced; D002302:Cardiac Output / Q000502:physiology; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D007362:Intensive Care Units / Q000592:standards; D008099:Liver / Q000502:physiology; D008297:Male; D010372:Pediatrics; D018079:Receptors, GABA / Q000187:drug effects; D000075462:Serum Albumin, Human / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D006993:Hypnotics and Sedatives; D018079:Receptors, GABA; D020927:Dexmedetomidine; D000075462:Serum Albumin, Human