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pharmacokinetics, ketamine

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
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
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
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
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
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
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
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
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
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
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
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
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
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
Marie-Chantal Giroux, Raphael Santamaria, Pierre Hélie, Patrick Burns, Francis Beaudry, Pascal Vachon
The main objective of this study was to compare the physiological changes (withdrawal and corneal reflexes, respiratory and cardiac frequency, blood oxygen saturation, and rectal temperature) following intraperitoneal administration of ketamine (80 mg/kg) and xylazine (10 mg/kg) to 3-, 6-, 12- and 18-month-old male Sprague Dawley rats (n=6/age group). Plasma pharmacokinetics, liver metabolism, and blood biochemistry were examined for a limited number of animals to better explain anesthetic drug effects. Selected organs were collected for histopathology...
2016: Experimental Animals
Paul A Tripi, Matthew E Kuestner, Connie S Poe-Kochert, Kasia Rubin, Jochen P Son-Hing, George H Thompson, Joseph D Tobias
INTRODUCTION: The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit...
2015: Journal of Pain Research
Margherita Bracchi, David Stuart, Richard Castles, Saye Khoo, David Back, Marta Boffito
Use of 'party drugs', a particular set of recreational drugs used in the context of 'ChemSex', is frequent among MSM living with HIV. A recently published observational study showed that more than half of HIV-infected MSM interviewed reported use of illicit substances in the previous 3 months, with frequent concomitant use of three or more drugs. These substances are a combination of 'club drugs' (methylenedioxymethamphetamine, gamma-hydroxybutyrate, ketamine, benzodiazepine) and drugs that are more specifically used in a sexualized context (methamphetamine, mephedrone, poppers and erectile dysfunction agents)...
August 24, 2015: AIDS
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
Francisco J Flores, ShiNung Ching, Katharine Hartnack, Amanda B Fath, Patrick L Purdon, Matthew A Wilson, Emery N Brown
OBJECTIVE: Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power...
October 2015: Journal of Neural Engineering
F J Couper, J J Saady
Drugs used to facilitate sexual assaults are typically those that rapidly render the potential victim unconscious or sedated, and produce memory loss or amnesia. Many of these drugs are difficult to detect due to a delay in biological specimen collection. Detection is further hampered as the drugs are often administered in single low doses and are rapidly and extensively metabolized, resulting in low concentrations in biological specimens. Miscellaneous prescription drugs such as the barbiturates, antipsychotics, opioids, tricyclic antidepressants, ketamine, and chloral hydrate have the potential to produce varying degrees of sedation; however, they are not frequently detected in drug-facilitated sexual assault cases...
January 2010: Forensic Science Review
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