Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine

Research output: Contribution to journalReview articlepeer-review

614 Citations (Scopus)
725 Downloads (Pure)

Abstract

Dexmedetomidine is an alpha(2)-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for alpha(2)-receptors with an alpha(2):alpha(1) ratio 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 alpha(2)-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.

Original languageEnglish
Pages (from-to)893-913
Number of pages21
JournalClinical Pharmacokinetics
Volume56
Issue number8
Early online date19-Jan-2017
DOIs
Publication statusPublished - Aug-2017

Keywords

  • MINIMUM ALVEOLAR CONCENTRATION
  • RANDOMIZED CONTROLLED-TRIAL
  • PLACEBO-CONTROLLED TRIAL
  • CRITICALLY-ILL PATIENTS
  • ALPHA(2)-ADRENOCEPTOR AGONIST DEXMEDETOMIDINE
  • INCREASING PLASMA-CONCENTRATIONS
  • LAPAROSCOPIC BARIATRIC SURGERY
  • ISCHEMIA-REPERFUSION INJURY
  • MINOR GYNECOLOGICAL SURGERY
  • HEALTHY MALE-VOLUNTEERS

Cite this