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dexmedetomidine pharmacokinetics

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...
January 19, 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 thirty 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 non-compartmental analyses or population modeling results are compared...
September 5, 2016: Drug Development and Industrial Pharmacy
Paweł Wiczling, Alicja Bartkowska-Śniatkowska, Oliwia Szerkus, Danuta Siluk, Jowita Rosada-Kurasińska, Justyna Warzybok, Agnieszka Borsuk, Roman Kaliszan, Edmund Grześkowiak, Agnieszka Bienert
The purpose of this study was to assess the pharmacokinetics of dexmedetomidine in the ICU settings during the prolonged infusion and to compare it with the existing literature data using the Bayesian population modeling with literature-based informative priors. Thirty-eight patients were included in the analysis with concentration measurements obtained at two occasions: first from 0 to 24 h after infusion initiation and second from 0 to 8 h after infusion end. Data analysis was conducted using WinBUGS software...
June 2016: Journal of Pharmacokinetics and Pharmacodynamics
Hua-Cheng Liu, Wei Sun, Cheng-Yu Wang, Wei-Yang Ying, Li-Dan Zheng, Rui-Feng Zeng, Zhe Wang, Ren-Shan Ge
A rapid, sensitive, and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution...
June 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Hua-Cheng Liu, Qing-Quan Lian, Fei-Fei Wu, Cheng-Yu Wang, Wei Sun, Li-Dan Zheng, Jürgen Schüttler, Harald Ihmsen
BACKGROUND AND OBJECTIVE: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients...
April 1, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Kristen M Messenger, Marie Hopfensperger, Heather K Knych, Mark G Papich
OBJECTIVE: To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. ANIMALS: 12 healthy adult dogs. PROCEDURES: In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment...
April 2016: American Journal of Veterinary Research
Jung Ju Choi, Ji Young Kim, Dongchul Lee, Young Jin Chang, Noo Ree Cho, Hyun Jeong Kwak
BACKGROUND: The pharmacokinetics and pharmacodynamics of an anesthetic drug may be influenced by gender. The purpose of this study was to compare effect-site half maximal effective concentrations (EC50) of propofol in male and female patients during i-gel insertion with dexmedetomidine 0.5 μg/kg without muscle relaxants. METHODS: Forty patients, aged 20-46 years of ASA physical status I or II, were allocated to one of two groups by gender (20 patients per group)...
March 22, 2016: BMC Anesthesiology
Mohamed Mahmoud, Keira P Mason
PURPOSE OF REVIEW: Over the past decade, the field of pediatric sedation has benefited from contributions which include the introduction and update of policies, procedures, and guidelines regarding training, physiologic monitoring and delivery, the approval of new sedatives, the multispecialty collaborations intended to advance the field and the development of sedatives, and delivery systems. This review will explore new drug innovations as well as evolved formulations of already approved agents, unique sedative delivery systems, the clinical application of pharmacogenetics and will conclude with a reflection on the current and future trends and focus of pediatric sedation research...
March 2016: Current Opinion in Anaesthesiology
Kyle J Schmidt, Mitesh R Doshi, Jenna M Holzhausen, Allycia Natavio, Megan Cadiz, Jim E Winegardner
OBJECTIVE: Approximately 50% of patients with alcohol dependence experience alcohol withdrawal. Severe alcohol withdrawal is characterized by seizures and/or delirium tremens, often refractory to standard doses of benzodiazepines, and requires aggressive treatment. This review aims to summarize the literature pertaining to the pharmacotherapy of severe alcohol withdrawal. DATA SOURCES: PubMed (January 1960 to October 2015) was searched using the search termsalcohol withdrawal, delirium tremens, intensive care, andrefractory Supplemental references were generated through review of identified literature citations...
May 2016: Annals of Pharmacotherapy
Yun Kuang, Yu-xia Xiang, Cheng-Xian Guo, Ran-ran Zhang, Guo- Ping Yang, Guan-feng Hou, Hong-yi Tan, Lu Huang, Jie Huang, Wen Ouyang, Kai-ming Duan, Sai-ying Wang, Jing-le Li, Qi Pei
OBJECTIVES: The objectives of this study were to construct a population pharmacokinetics model for dexmedetomidine used in Chinese adult patients with spinal anesthesia and to identify the key factors affecting the pharmacokinetics of dexmedetomidine. METHODS: A total of 34 subjects (elderly group: n = 15; young group: n = 19) undergoing spinal anesthesia received dexmedetomidine with a loading dose of 0.5 μg×kg(-1) for 10 minutes, followed by a maintenance dose of 0...
March 2016: International Journal of Clinical Pharmacology and Therapeutics
R C Bennett, K M Salla, M R Raekallio, L Hänninen, V M Rinne, M Scheinin, O M Vainio
We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 μg/kg) or medetomidine with MK-467 (250 μg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb...
August 2016: Journal of Veterinary Pharmacology and Therapeutics
Wenhua Zhang, Zixin Wang, Xingrong Song, Yanting Fan, Hang Tian, Bilian Li
BACKGROUND: Chloral hydrate, a commonly used sedative in children during noninvasive diagnostic procedures, is associated with side effects like prolonged sedation, paradoxical excitement, delirium, and unpleasant taste. Dexmedetomidine, a highly selective α-2 agonist, has better pharmacokinetic properties than chloral hydrate. We conducted this prospective, double-blind, randomized controlled trial to evaluate efficacy of intranasal dexmedetomidine with that of a second oral dose of chloral hydrate for rescue sedation during magnetic resonance imaging (MRI) studies in infants...
March 2016: Paediatric Anaesthesia
Mihaela Damian, Gregory Hammer, Mohammed El-Komy, Adam Frymoyer, David Drover, Felice Su
No abstract text is available yet for this article.
December 2015: Critical Care Medicine
Yun Kuang, Ran-Ran Zhang, Qi Pei, Hong-Yi Tan, Cheng-Xian Guo, Jie Huang, Yu-Xia Xiang, Wen Ouyang, Kai-Ming Duan, Sai-Ying Wang, Guo-Ping Yang
OBJECTIVE: The application of dexmedetomidine in patient sedation is generally accepted, though its clinical application is limited because of the lack of information detailing the specific properties among diverse populations of patients. The aim of this study was to compare the pharmacokinetic and pharmacodynamic characteristics of dexmedetomidine between elderly and young patients during spinal anesthesia. METHODS: 34 subjects (elderly group: n = 15; young group: n = 19) with spinal anesthesia were enrolled in the present study following the inclusion/exclusion criteria detailed below...
December 2015: International Journal of Clinical Pharmacology and Therapeutics
Luis I Cortínez, Brian J Anderson, Nick H G Holford, Valentina Puga, Natalia de la Fuente, Hernán Auad, Sandra Solari, Fidel A Allende, Mauricio Ibacache
PURPOSE: This study aims to characterize the influence of body weight and composition on the pharmacokinetics of dexmedetomidine. METHODS: Twenty obese patients and 20 non-obese patients scheduled for elective laparoscopic surgery were given dexmedetomidine infusion schemes. Venous blood samples were taken during and after dexmedetomidine administration. Population pharmacokinetic modeling was undertaken to investigate fat free mass (FFM) and normal fat mass (NFM) as size descriptors of volumes and clearances using non-linear mixed effects modeling...
December 2015: European Journal of Clinical Pharmacology
Janelle D Vaughns, Victoria C Ziesenitz, John N van den Anker
Obesity represents one of the most important public health issues according to the World Health Organization. Additionally, in a recent National Health and Nutrition Survey of 2011-2012, approximately 17 % of children and adolescents in the United States were considered obese. The obesity rate is higher within the adolescent age group as compared to preschool children. Childhood obesity is particularly problematic, because the co-morbid disease states which accompany obesity may require frequent pharmacotherapy and/ or surgical intervention...
2015: Current Pharmaceutical Design
Ting Zhang, Yuxiao Deng, Ping He, Zhengyu He, Xiangrui Wang
STUDY OBJECTIVE: To explore the effects of mild hypoalbuminemia on pharmacokinetics and pharmacodynamics of dexmedetomidine in patients after major abdominal or thoracic surgery. DESIGN: A prospective cohort study. SETTING: University-affiliated teaching hospital. PATIENTS: The study was performed in 30 consecutive patients undergoing major abdominal or thoracic surgery. They were aged 18 to 65 years and graded as American Society of Anesthesiologists physical status I and II...
December 2015: Journal of Clinical Anesthesia
Heedoo Yoo, Timo Iirola, Sanna Vilo, Tuula Manner, Riku Aantaa, Maria Lahtinen, Mika Scheinin, Klaus T Olkkola, William J Jusko
PURPOSE: Dexmedetomidine is an α2-adrenoceptor agonist used for perioperative and intensive care sedation. This study develops mechanism-based population pharmacokinetic-pharmacodynamic models for the cardiovascular and central nervous system (CNS) effects of intravenously (IV) and intranasally (IN) administered dexmedetomidine in healthy subjects. METHOD: Single doses of 84 μg of dexmedetomidine were given once IV and once IN to six healthy men. Plasma dexmedetomidine concentrations were measured for 10 h along with plasma concentrations of norepinephrine (NE) and epinephrine (E)...
October 2015: European Journal of Clinical Pharmacology
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