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dexmedetomidine pharmacokinetics

Pekka Talke, Brian J Anderson
AIMS: Alpha-2 agonists are direct peripheral vasoconstrictors by activation of vascular smooth muscle alpha-2 adrenoceptors. The impact of this response during dexmedetomidine infusion remains poorly quantified. Our goal was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD, vasoconstriction) effects of a computer controlled dexmedetomidine infusion in healthy volunteers. METHODS: After local ethics committee approval, we studied 10 healthy volunteers...
March 1, 2018: British Journal of Clinical Pharmacology
J Benito, B Monteiro, F Beaudry, P Steagall
No abstract text is available yet for this article.
September 2017: Veterinary Anaesthesia and Analgesia
Guo-Rong He, Xiao-Kun Lin, Yong-Biao Wang, Cong-De Chen
Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic P‑glycoprotein (P‑gp) serves a critical role in the disposition of drugs, the present study aimed to address whether P‑gp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and P‑gp function was evaluated by the intracellular accumulation of Rhodamine 123...
February 2, 2018: Molecular Medicine Reports
Piotr Smuszkiewicz, Paweł Wiczling, Justyna Ber, Justyna Warzybok, Tomasz Małkiewicz, Jan Matysiak, Agnieszka Klupczyńska, Iwona Trojanowska, Zenon Kokot, Edmund Grześkowiak, Wojciech Krzyzanski, Agnieszka Bienert
Dexmedetomidine (DEX) is a fairly new alfa2-agonist which has been increasingly used in recent years for analgosedation, mostly because it offers a unique ability of providing both moderate level of sedation and analgesia without respiratory depression. Despite of many papers published, there are still only a few concerning the PK of the drug given as long-term infusion in ICU patients. The aim of this work was to characterize the population pharmacokinetics of dexmedetomidine and to investigate the potential benefits of individualization of drug dosing based on patient characteristics in the heterogeneous group of medical and surgical patients staying in intensive care unit...
December 30, 2017: Journal of Pharmacokinetics and Pharmacodynamics
W Zhong, Y Zhang, M-Z Zhang, X-H Huang, Y Li, R Li, Q-W Liu
WHAT IS KNOWN AND OBJECTIVE: The primary objective of this study was to compare the pharmacokinetics of dexmedetomidine in patients with end-stage renal failure and secondary hyperparathyroidism with those in normal individuals. METHOD: Fifteen patients with end-stage renal failure and secondary hyperparathyroidism (Renal-failure Group) and 8 patients with normal renal and parathyroid gland function (Control Group) received intravenous 0.6 μg/kg dexmedetomidine for 10 minutes before anaesthesia induction...
December 16, 2017: Journal of Clinical Pharmacy and Therapeutics
M Gozalo-Marcilla, F Gasthuys, S P L Luna, S Schauvliege
The objective of this review was to perform a literature compilation of all the equine publications that used dexmedetomidine as the first article on this topic was published, in 2005. We also aimed to answer the question whether the use of dexmedetomidine can currently be justified. For that, we compiled information from databases, such as PubMed, Google Scholar and Web of Science and the proceedings of the last veterinary anaesthesiology meetings. Dexmedetomidine is an attractive drug to be used in horses, mainly due to its pharmacokinetic profile and pharmacodynamics that favour its use as intravenous constant rate infusion (CRI)...
April 2018: Journal of Veterinary Pharmacology and Therapeutics
Joshua H Atkins, Jeff E Mandel
PURPOSE OF REVIEW: Provide a practical update on drug-induced sleep endoscopy (DISE) for anesthesia providers, which can also serve as a reference for those preparing to establish a DISE program. RECENT FINDINGS: New developments in surgical approaches to OSA and the growing global incidence of the condition have stimulated increased interest and demand for drug-induced sleep endoscopy. New techniques include transoral robotic surgery and hypoglossal nerve stimulation...
February 2018: Current Opinion in Anaesthesiology
Shinju Obara, Tsuyoshi Imaizumi, Takahiro Hakozaki, Atsuyuki Hosono, Yuzo Iseki, Norie Sanbe, Masahiro Murakawa
PURPOSE: Little information is available on the predictive ability of previously published pharmacokinetic models of dexmedetomidine in patients under spinal anesthesia. We evaluated nine published pharmacokinetic models that were constructed in different study settings. METHODS: Sixteen patients received dexmedetomidine infusions after spinal anesthesia according to the manufacturer's recommended regimen (6 µg/kg/h over 10 min followed by 0.2-0.7 µg/kg/h) or target-controlled infusion (initial target of 1...
November 2, 2017: Journal of Anesthesia
Alyssa Zhu, Hubert A Benzon, T Anthony Anderson
While a large number of studies has examined the efficacy of opioid-sparing analgesics in adult surgical populations, fewer studies are available to guide postoperative pain treatment in pediatric patients. We systematically reviewed available publications on the use of systemic nonopioid agents for postoperative analgesia in pediatric surgical populations. A comprehensive literature search identified meta-analyses and randomized controlled trials (RCTs) assessing the effects of systemic, nonopioid agents on postoperative narcotic requirements or pain scores in pediatric surgical populations...
November 2017: Anesthesia and Analgesia
P J Colin, L N Hannivoort, D J Eleveld, K M E M Reyntjens, A R Absalom, H E M Vereecke, M M R F Struys
Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate. Methods: Dexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model...
August 1, 2017: British Journal of Anaesthesia
P J Colin, L N Hannivoort, D J Eleveld, K M E M Reyntjens, A R Absalom, H E M Vereecke, M M R F Struys
Background: Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. Methods: In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model...
August 1, 2017: British Journal of Anaesthesia
Bo Xu, Dongxu Zhou, Li Ren, Steven Shulman, Xingan Zhang, Ming Xiong
BACKGROUND: This study was designed to investigate the pharmacokinetics and pharmacodynamics of dexmedetomidine in morbidly obese patients undergoing laparoscopic surgery. METHODS: Morbidly obese (body mass index ≥40 kg/m(2)) and normal weight patients scheduled for elective laparoscopic surgery were included (n = 8, each group). After baseline hemodynamic measurement, dexmedetomidine 1 μg/kg was administered over 10 min. General anesthesia was induced with propofol 1...
December 2017: Journal of Anesthesia
Bruno H Pypendop, Juhana Honkavaara, Jan E Ilkiw
OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. STUDY DESIGN: Prospective randomized crossover experimental study. ANIMALS: A total of eight healthy adult male castrated cats aged 1-2 years. METHODS: Cats were administered dexmedetomidine (25 μg kg(-1)) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg(-1)) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg(-1)) IM with 300, 600 or 1200 μg kg(-1) MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM)...
April 9, 2017: Veterinary Anaesthesia and Analgesia
Ryan S Bailey, Linda S Barter, Bruno H Pypendop
OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine when administered as a short intravenous (IV) infusion to isoflurane-anesthetized rabbits. STUDY DESIGN: Experimental study. ANIMALS: A total of six healthy adult female New Zealand White rabbits. METHODS: Rabbits were anesthetized with isoflurane in oxygen. Following determination of isoflurane minimum alveolar concentration (MAC), the anesthetic dose was reduced to 0...
March 6, 2017: Veterinary Anaesthesia and Analgesia
Amin Davoudi, Bijan Movahedian Attar, Elham Shadmehr
Oral and maxillofacial surgeries might induce anxiety and pain to the patients. Sedative agents are one of the best ways for eliminating such consequences. Dexmedetomidine (DEX) is a recent sedative agent which presents higher sedative quality with greater specificity than other drugs. The aim of present paper is to evaluate the risks and benefits of administrating DEX during oral and maxillofacial surgeries by reviewing high quality released articles. Areas covered: Searches on PubMed, Scopus and Web of Science databases were completed with focus on randomized controlled trials (RCT)...
June 2017: Expert Opinion on Drug Safety
Rachel G Greenberg, Huali Wu, Matthew Laughon, Edmund Capparelli, Stevie Rowe, Kanecia O Zimmerman, P Brian Smith, Michael Cohen-Wolkowiez
Despite limited pharmacokinetic (PK) data, dexmedetomidine is increasingly being used off-label for sedation in infants. We aimed to characterize the developmental PK changes of dexmedetomidine during infancy. In this open-label, single-center PK study of dexmedetomidine in infants receiving dexmedetomidine per clinical care, ≤10 blood samples per infant were collected. A set of structural PK models and residual error models were explored using nonlinear mixed-effects modeling in NONMEM. Covariates including postmenstrual age (PMA), serum creatinine, and recent history of cardiac surgery requiring cardiopulmonary bypass were investigated for their influence on PK parameters...
September 2017: Journal of Clinical Pharmacology
Oliwia Szerkus, Wiktoria Struck-Lewicka, Marta Kordalewska, Ewa Bartosińska, Renata Bujak, Agnieszka Borsuk, Agnieszka Bienert, Alicja Bartkowska-Śniatkowska, Justyna Warzybok, Paweł Wiczling, Antoni Nasal, Roman Kaliszan, Michał Jan Markuszewski, Danuta Siluk
AIM: The purpose of this work was to develop and validate a rapid and robust LC-MS/MS method for the determination of dexmedetomidine (DEX) in plasma, suitable for analysis of a large number of samples. METHOD: Systematic approach, Design of Experiments, was applied to optimize ESI source parameters and to evaluate method robustness, therefore, a rapid, stable and cost-effective assay was developed. The method was validated according to US FDA guidelines. LLOQ was determined at 5 pg/ml...
February 2017: Bioanalysis
Maud A S Weerink, Michel M R F Struys, Laura N Hannivoort, Clemens R M Barends, Anthony R Absalom, Pieter Colin
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...
August 2017: Clinical Pharmacokinetics
P Cagnardi, R Villa, G Ravasio, L Lucatello, F Di Cesare, F Capolongo, A Boccardo, D Pravettoni
AIMS: To evaluate the pharmacokinetics of dexmedetomidine (DEX) administered I/V at a dose of 5 µg/kg bodyweight in dairy calves and to compare the sedative effects of anaesthetic protocols involving DEX and xylazine. METHODS: Nine dairy calves, aged 17-20 days, were treated with 5 µg/kg I/V dexmedetomidine. For pharmacokinetic evaluation, blood samples were collected over 12 hours and serum samples were analysed by high performance liquid chromatography-mass spectrometry...
January 2017: New Zealand Veterinary Journal
Aiwei Li, Vivian Man Ying Yuen, Sophie Goulay-Dufay, Philip Chi Lip Kwok
Dexmedetomidine is an alpha-2 adrenoceptor agonist and has been used as a general anesthetic, sedative and analgesic for about 30 years. The aim of this paper is to review the pharmacokinetics and pharmacodynamics of dexmedetomidine, evaluate physiological factors that may affect the pharmacokinetics of dexmedetomidine, and summarize the pharmacodynamics of dexmedetomidine at different plasma levels. The pharmacokinetic parameters reported in previous studies according to noncompartmental analyses or population modeling results are compared...
December 2016: Drug Development and Industrial Pharmacy
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