dexmedetomidine pharmacokinetics

INTRODUCTION: Especially when acutely ill, individuals with schizophrenia and bipolar disorder can present with agitated behavior. The initial approach to agitation management are non-pharmacologic strategies such as verbal de-escalation techniques; however, pharmacologic interventions may be needed. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist, and a sublingual formulation has been approved in the US for the treatment of agitation associated with schizophrenia and bipolar disorder in adults...

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support...

BACKGROUND: Cardiopulmonary bypass can affect the pharmacokinetics of anesthetic agents. AIMS: We aimed to evaluate the pharmacokinetics of dexmedetomidine for infants and small children undergoing cardiac surgery with cardiopulmonary bypass based on population pharmacokinetics. METHODS: We enrolled 30 pediatric cardiac surgical patients in this study. After anesthetic induction with atropine (0.02 mg/kg), thiopental sodium (5 mg/kg), and fentanyl (2-3 μg/kg), we administered 1 μg/kg of dexmedetomidine for 10 min, followed by administration of 0...

The purpose of this study was to prepare a dexmedetomidine (Dex) 72 h long-acting patch by the combined use of ion-pair strategy and chemical enhancers (CEs), and to investigate molecular mechanisms of drug-loading enhancement and controlled release. The formulation of patch was optimized by single-factor investigation and Box-Behnken design. The pharmacokinetics, analgesic pharmacodynamics and irritation of the formulation were evaluated, respectively. Moreover, the effects of ion-pairs and CEs on the patch were characterized by DSC, rheology study, FTIR, and molecular docking, and the effects on the skin were evaluated by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman study, and molecular dynamics, respectively...

INTRODUCTION: Dexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59-67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates. METHODS: The TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicentre, superiority trial comparing neurological outcome after standard sevoflurane anaesthesia with dexmedetomidine/remifentanil and low dose sevoflurane anaesthesia in children aged less than 2 years undergoing anaesthesia of 2 hours or longer...

Dexmedetomidine's unique sedative properties have led to its widespread use. Dexmedetomidine has a beneficial pharmacologic profile including analgesic sparing effects, anxiolysis, sympatholysis, organ-protective effects against ischemic and hypoxic injury, and sedation which parallels natural sleep. An understanding of predictable side effects, effects of age-related physiologic changes, and pharmacokinetic and pharmacodynamic effects of dexmedetomidine is crucial to maximize its safe administration in adults and children...

Mechanical ventilation is an uncomfortable and potentially painful intervention. Opioids, such as morphine and fentanyl, are used for analgesia and sedation but there is uncertainty whether they reduce pain in mechanically ventilated infants. Moreover, there may be short-term and long-term adverse consequences such as respiratory depression leading to prolonged mechanical ventilation and detrimental long-term neurodevelopmental effects. Despite this, opioids are widely used, possibly due to a lack of alternatives...

Background: Dexmedetomidine is a commonly used clinical sedative; however, the drug response varies among individuals. Thus, the purpose of this study was to explore the association between dexmedetomidine response and gene polymorphisms related to drug-metabolizing enzymes and drug response ( CYP2A6 , UGT2B10 , UGT1A4 , ADRA2A , ADRA2B , ADRA2C , GABRA1 , GABRB2 , and GLRA1 ). Methods: This study was a prospective cohort study. A total of 194 female patients aged 18-60 years, American Society of Anesthesiologists (ASA) score I-II, who underwent laparoscopy at the Third Xiangya Hospital of Central South University, were included...

Background: Dexmedetomidine is a sedative and analgesic increasingly used in children supported with extracorporeal membrane oxygenation (ECMO). No data is available to describe the pharmacokinetics (PK) of dexmedetomidine in this population. Methods: We performed a single-center prospective PK study. Children <18 years old, supported with ECMO, and on a dexmedetomidine infusion as part of their management were prospectively included. PK samples were collected...

OBJECTIVE: Dexmedetomidine has been introduced in emergence coughing, agitation, and shivering prevention. This study aimed to investigate the optimal dose of dexmedetomidine for emergence cough prophylaxis. METHODS: In this randomized, double-blinded, and prospective trial, 356 patients scheduled for an endovascular interventional procedure were randomly assigned to 0.3 (D 0.3), 0.4 (D 0.4), 0.5 (D 0.5), and 0.6 (D 0.6) μg·kg-1 ·h-1 dexmedetomidine rate, or saline control (C), from anesthesia induction until the end of surgery...

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children. Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray...

Sedative use can result in adverse drug reactions. Intensive care unit patients are especially at risk and pharmacokinetic modeling of drug concentrations is an approach to develop precision dosing strategies. However, limited blood sampling availability in critically ill children and need for multiple assays to quantify a variety of commonly used sedatives creates logistical challenges. The goal of this project was to develop a sensitive and selective assay for the simultaneous quantification of a panel of sedatives comprised of midazolam (MDZ), alpha hydroxymidazolam (1- OH MDZ), dexmedetomidine (DEX), morphine (MOR), morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), fentanyl (FEN), norfentanyl (NF), and hydromorphone (HM) in small volume pediatric plasma samples...

Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative-analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens ( n = 6/group) aged between 6 and 8 weeks...

Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population...

This study investigated the cardiopulmonary effects and pharmacokinetics of dexmedetomidine (DEX) used as an adjunctive analgesic for regional anesthesia of the oral cavity with levobupivacaine in anesthetized dogs. Forty dogs were randomly assigned to four groups of 10 dogs. All dogs received levobupivacaine (4 blocks) with DEX IO (infraorbital block, n = 10) or IA (inferior alveolar block, n = 10) or placebo (PLC; n = 10) or DEX ( n = 10) was injected intravenously (IV) after administration of levobupivacaine...

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis. Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery. Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019 were included...

BACKGROUND: Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old. METHODS: Intranasal dexmedetomidine 2 µg · kg-1 was administered to children with simple vascular malformations undergoing interventional radiological procedures...

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS...

BACKGROUND: Atomized intranasal dexmedetomidine is an attractive option when sedation is required for pediatric patients as either premedication or the sole agent for noninvasive, nonpainful procedures. While intranasal dexmedetomidine is used frequently in this population, it is still unclear what dose and time of administration relative to the procedure will result in the optimal effect. Knowledge regarding the maximum concentration (C max ) and time to reach maximum concentration (T max ) of intranasally administered dexmedetomidine is the first step toward this...

BACKGROUND: Dexmedetomidine is currently off-label for use in pediatric clinical care worldwide. Nevertheless, it is frequently prescribed to pediatric patients as premedication prior to induction of anesthesia or for procedural sedation. There is ample literature on the pharmacokinetics, efficacy and safety of dexmedetomidine in this vulnerable patient population, but there is a general lack of consensus on dosing. In this project, we aimed to use the standardized workflow of the Dutch Pediatric Formulary to establish best evidence-based pediatric dosing guidelines for dexmedetomidine as premedication and for procedural sedation...