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:α1 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 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.

Using target-controlled infusion in healthy volunteers, the pharmacokinetics of dexmedetomidine were best described by a three-compartment allometric model. Apart from weight, no other covariates were identified.

NCT01879865.

NCT01879865.

No abstract

The triple interaction model estimates the potency of any combination of sevoflurane, propofol, and remifentanil expressed as either PTOL or NSRI.

By combining pre- and poststimulation data, interaction models for BIS, SE, and RE demonstrate a consistent influence of "stimulation" on the pharmacodynamic relationship between sevoflurane and remifentanil. Significant population variability exists for Composite Variability Index and Surgical Pleth Index.

Purpose of reviewGrowing concerns about the environmental effects of volatile anaesthetics are likely to lead to increased use of intravenous anaesthetic drugs. Pharmacokinetic/pharmacodynamic (PKPD) models can increase the accuracy of intravenous drug titration, especially in populations that differ from the 'average.' However, with a growing number of PKPD models, and other technology available to date, it can be hard to see the wood for the trees. This review attempts to guide the reader through the PKPD jungle. Recent findingsGeneral purpose PKPD models for propofol and remifentanil designed to apply to a broader population, including children, the elderly and the obese, reduce the need for population-specific models. PKPD models for drugs such as dexmedetomidine and antimicrobial agents may be useful for procedural sedation or in the ICU. Technological advances such as Bayesian model adjustment based on point-of-care plasma concentration measurements, closed-loop drug delivery and artificial intelligence may improve the ease of use of the anaesthetic drugs and increase the accuracy of titration. SummaryNewer and more complex modelling techniques and technological advancements can help to deliver anaesthetic drugs, sedatives and other drugs in a more stable and thereby safer way.