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Ketamine, pharmacokinetics

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https://www.readbyqxmd.com/read/28521255/pharmacokinetics-of-ketamine-and-norketamine-enantiomers-after-racemic-or-s-ketamine-iv-bolus-administration-in-dogs-during-sevoflurane-anaesthesia
#1
Noemi Romagnoli, Rima N Bektas, Annette P Kutter, Andrea Barbarossa, Paola Roncada, Sonja Hartnack, Regula Bettschart-Wolfensberger
The aims of this study were to measure plasma levels of R- and S-ketamine and their major metabolites R- and S-norketamine following single intravenous bolus administration of racemic or S-ketamine in sevoflurane anaesthetised dogs and to calculate the relevant pharmacokinetic profiles. Six adult healthy beagle dogs were used in the study. An intravenous bolus of 4mg/kg racemic ketamine (RS-KET) or 2mg/kg S-ketamine (S-KET) was administered, with a three-weeks washout period between treatments. Venous blood samples were collected at fixed times until 900min and R- and S-ketamine as well as R- and S-norketamine plasma levels determined by liquid chromatography coupled with tandem mass spectrometry...
May 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28492297/recent-anti-seizure-medications-in-the-intensive-care-unit
#2
Cindy Orinx, Benjamin Legros, Nicolas Gaspard
BACKGROUND: Seizures and status epilepticus (SE), both clinical and subclinical, are frequent in critically ill patients. The list of available anti-seizure medications (ASMs) is expanding and now includes older and widely used drugs as well as more recent medications with a better safety and pharmacokinetics profile. METHODS: We review a selection of recent publications about the indications and administration of ASMs in critical care for the prophylaxis and treatment of seizures and SE, focusing on recent ASMs available as intravenous formulation and emphasizing pharmacokinetics and safety issues in relation to several aspects of critical illness...
May 11, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28339766/higher-bioavailability-of-doxycycline-in-broiler-chickens-with-a-novel-in-feed-pharmaceutical-formulation
#3
Lilia Gutiérrez, Juan Zermeño, Yazmín Alcalá, Héctor Sumano
Bioavailability of a new, long-acting (LA) pharmaceutical preparation for administering doxycycline as in-feed medication to broiler chickens was compared to the standard in-feed administration of doxycycline. A commercial poultry house harboring Ross-308 broiler chickens, weighing 450 g, was divided into 7 sections as follows: doxy-FOLA group (n = 6,000 chickens divided into 3 replicates) medicated with 10% doxycyline, long-acting pellets at a dose of 400 g of doxycycline HCl/ton of food, resulting in a calculated dose of 48 mg/kg for 5 d; doxy-ref group (n = 6,000, divided into 3 replicates) medicated as for doxy-FOLA, but using a 20% commercial preparation of doxycycline...
February 23, 2017: Poultry Science
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#4
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28065587/ffpm-a-pde4-inhibitor-reverses-learning-and-memory-deficits-in-app-ps1-transgenic-mice-via-camp-pka-creb-signaling-and-anti-inflammatory-effects
#5
Haibiao Guo, Yufang Cheng, Canmao Wang, Jingang Wu, Zhengqiang Zou, Bo Niu, Hui Yu, Haitao Wang, Jiangping Xu
Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27888525/breaking-sad-unleashing-the-breakthrough-potential-of-ketamine-s-rapid-antidepressant-effects
#6
David Feifel
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h...
December 2016: Drug Development Research
https://www.readbyqxmd.com/read/27763887/role-of-cytochrome-p4502b6-polymorphisms-in-ketamine-metabolism-and-clearance
#7
Lesley K Rao, Alicia M Flaker, Christina C Friedel, Evan D Kharasch
BACKGROUND: At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro...
December 2016: Anesthesiology
https://www.readbyqxmd.com/read/27578365/ketamine-dependent-neuronal-activation-in-healthy-volunteers
#8
Anna Höflich, Andreas Hahn, Martin Küblböck, Georg S Kranz, Thomas Vanicek, Sebastian Ganger, Marie Spies, Christian Windischberger, Siegfried Kasper, Dietmar Winkler, Rupert Lanzenberger
Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S(®)) was administered intravenously to 35 healthy volunteers...
August 30, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27485149/pharmacokinetics-of-ketamine-and-three-metabolites-in-beagle-dogs-under-sevoflurane-vs-medetomidine-comedication-assessed-by-enantioselective-capillary-electrophoresis
#9
Friederike A Sandbaumhüter, Regula Theurillat, Rima N Bektas, Annette P N Kutter, Regula Bettschart-Wolfensberger, Wolfgang Thormann
Ketamine is often used for anesthesia in veterinary medicine. One possible comedication is the sedative α2-agonist medetomidine. Advantages of that combination are the compensation of side effects of the two drugs and the anesthetic-sparing effect of medetomidine. In vitro studies showed that medetomidine has an inhibitive effect on the formation of norketamine. Norketamine is the first metabolite of ketamine and is also active. It is followed by others like 6-hydroxynorketamine and 5,6-dehydronorketamine (DHNK)...
October 7, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27330369/pain-and-anxiety-management-for-pediatric-dental-procedures-using-various-combinations-of-sedative-drugs-a-review
#10
REVIEW
Giath Gazal, Wamiq Musheer Fareed, Muhammad Sohail Zafar, Khalid H Al-Samadani
For fearful and uncooperative children behavioral management techniques are used. In order to control the pain and anxiety in pedodontic patients, pharmacologic sedation, anesthesia and analgesia are commonly used. Midazolam is commonly used as an oral sedation agent in children; it has several features such as safety of use, quick onset and certain degree of amnesia that makes it a desirable sedation agent in children. This review paper discusses various aspects of oral midazolam, ketamine and their combinations in conscious sedation including, advantages of oral route of sedation, pharmacokinetics, range of oral doses, and antagonists for clinical dental treatment procedures...
July 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/27263962/physiological-and-pharmacokinetic-effects-of-multilevel-caging-on-sprague-dawley-rats-under-ketamine-xylazine-anesthesia
#11
Aurore Dodelet-Devillers, Chiara Zullian, Francis Beaudry, Jim Gourdon, Julie Chevrette, Pierre Hélie, Pascal Vachon
While the cage refinement is a necessary step towards improving the welfare of research rats, increasing the complexity and surface area of the living space of an animal may have physiological impacts that need to be taken into consideration. In this study, ketamine (80 mg/kg) and xylazine (10 mg/kg) caused a short duration anesthesia that was significantly decreased in Sprague-Dawley rats housed in multilevel cages (MLC), compared to rats housed in standard cages (SDC). The withdrawal reflex, the palpebral reflexes and the time-to-sternal all occurred earlier in MLC housed rats, suggesting an effect of housing on the physiology of the rats...
November 1, 2016: Experimental Animals
https://www.readbyqxmd.com/read/27155360/detailed-pharmacological-evaluation-of-methoxetamine-mxe-a-novel-psychoactive-ketamine-analogue-behavioural-pharmacokinetic-and-metabolic-studies-in-the-wistar-rat
#12
Rachel R Horsley, Eva Lhotkova, Katerina Hajkova, Bronislav Jurasek, Martin Kuchar, Tomas Palenicek
Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its toxicity; therefore we tested, in Wistar rats, the effects of MXE in a series of behavioural tasks, measured its pharmacokinetics and urinary metabolites. Locomotor activity and its spatial characteristics (in the open field) and sensorimotor gating (prepulse inhibition; PPI) were evaluated after 5, 10 and 40mg/kg subcutaneous (sc...
May 4, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27044652/evaluation-and-optimisation-of-propofol-pharmacokinetic-parameters-in-cats-for-target-controlled-infusion
#13
A Cattai, T Pilla, P Cagnardi, A Zonca, P Franci
The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective neutering of seven healthy cats, premedicated intramuscularly with 0.3 mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood samples were collected over 240 minutes, and propofol concentrations were measured via a validated high-performance liquid chromatography assay...
May 14, 2016: Veterinary Record
https://www.readbyqxmd.com/read/27028535/ketamine-a-review-of-clinical-pharmacokinetics-and-pharmacodynamics-in-anesthesia-and-pain-therapy
#14
REVIEW
Marko A Peltoniemi, Nora M Hagelberg, Klaus T Olkkola, Teijo I Saari
Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers. It undergoes oxidative metabolism, mainly to norketamine by cytochrome P450 (CYP) 3A and CYP2B6 enzymes. The use of S-ketamine is increasing worldwide, since the S(+)-enantiomer has been postulated to be a four times more potent anesthetic and analgesic than the R(-)-enantiomer and approximately two times more effective than the racemic mixture of ketamine...
September 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27018176/ketamine-use-in-current-clinical-practice
#15
REVIEW
Mei Gao, Damoon Rejaei, Hong Liu
After nearly half a century on the market, ketamine still occupies a unique corner in the medical armamentarium of anesthesiologists or clinicians treating pain. Over the last two decades, much research has been conducted highlighting the drug's mechanisms of action, specifically those of its enantiomers. Nowadays, ketamine is also being utilized for pediatric pain control in emergency department, with its anti-hyperalgesic and anti-inflammatory effects being revealed in acute and chronic pain management. Recently, new insights have been gained on ketamine's potential anti-depressive and antisuicidal effects...
July 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27017097/subchronic-administration-of-r-s-ketamine-induces-ketamine-ring-hydroxylation-in-wistar-rats
#16
R Moaddel, M Sanghvi, A Ramamoorthy, K Jozwiak, N Singh, C Green, K O'Loughlin, M Torjman, I W Wainer
Subchronic administration of (R,S)-ketamine, (R,S)-Ket, is used in the treatment of neuropathic pain, in particular Complex Regional Pain Syndrome, but the effect of this protocol on the metabolism of (R,S)-Ket is unknown. In this study, daily administration of a low dose of (R,S)-Ket for 14-days to Wistar rats was conducted to determine the impact of sub-chronic dosing on the pharmacokinetics of (R,S)-Ket and its major metabolites. The data indicate that, relative to a single administration of (R,S)-Ket, subchronic administration resulted in increased clearance of (R,S)-Ket and the N-demethylated metabolite norketamine measured as elimination half-life (t1/2) and decreased plasma concentrations of these compounds...
August 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/26926335/a-forecast-of-relevant-pediatric-sedation-trends
#17
REVIEW
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
https://www.readbyqxmd.com/read/26861990/treatment-of-severe-alcohol-withdrawal
#18
REVIEW
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
https://www.readbyqxmd.com/read/26661185/quantification-of-the-novel-n-methyl-d-aspartate-receptor-ligand-11c-gmom-in-man
#19
Thalia F van der Doef, Sandeep Sv Golla, Pieter J Klein, Gisela M Oropeza-Seguias, Robert C Schuit, Athanasios Metaxas, Ellen Jobse, Lothar A Schwarte, Albert D Windhorst, Adriaan A Lammertsma, Bart Nm van Berckel, Ronald Boellaard
[(11)C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N'-(3-[(11)C]methoxy-phenyl)-N'-methylguanidine) is a PET ligand that binds to the N-methyl-d-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [(11)C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [(11)C]GMOM PET scans were obtained from 10 subjects...
June 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/26644333/long-term-effect-of-sub-anesthetic-ketamine-in-reducing-l-dopa-induced-dyskinesias-in-a-preclinical-model
#20
Mitchell J Bartlett, Ria M Joseph, Lindsey M LePoidevin, Kate L Parent, Nicholas D Laude, Levi B Lazarus, Michael L Heien, Miguel Estevez, Scott J Sherman, Torsten Falk
Low-dose sub-anesthetic ketamine infusion treatment has led to a long-term reduction of treatment-resistant depression and posttraumatic stress disorder (PTSD) symptom severity, as well as reduction of chronic pain states, including migraine headaches. Ketamine also is known to change oscillatory electric brain activity. One commonality between migraine headaches, depression, PTSD, Parkinson's disease (PD) and l-DOPA-induced dyskinesias (LID) is hypersynchrony of electric activity in the brain, including the basal ganglia...
January 26, 2016: Neuroscience Letters
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