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Ketamine, pharmacokinetics

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https://www.readbyqxmd.com/read/29458790/non-pharmacological-interventions-and-non-fentanyl-pharmacological-treatments-for-breakthrough-cancer-pain-a-systematic-and-critical-review
#1
REVIEW
Sebastiano Mercadante
BACKGROUND: Oral opioids or other pharmacological or non-pharmacological interventions are often suggested in the management of breakthrough cancer pain (BTcP). The aim of this systematic and critical review was to analyse and critically comment the evidence of any non-fentanyl therapies proposed for BTcP. METHODS: A systematic literature search was carried out to find studies providing clinical data on any treatment excluding fentanyl products. RESULTS: No data exist about the use of oral opioids...
February 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29396996/intranasal-ketamine-and-its-potential-role-in-cancer-related-pain
#2
Vinita Singh, Theresa W Gillespie, R Donald Harvey
Cancer-related pain continues to be a significant therapeutic challenge, made more difficult by contemporary opioid use and diversion concerns. Conventional treatment utilizing a tiered approach of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvant agents is limited; and alternatives are needed for patients with rapidly progressing pain and those who develop hyperalgesia and tolerance to opioids. Ketamine, an N-methyl-D-aspartate (NMDA) selective antagonist, has historically been used for anesthesia in adult and pediatric populations, but has also been investigated for depression, bipolar disorder, and general and post-operative pain management...
February 3, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29229209/randomized-double-blind-placebo-controlled-dose-escalation-study-investigation-of-the-safety-pharmacokinetics-and-antihyperalgesic-activity-of-l-4-chlorokynurenine-in-healthy-volunteers
#3
Mark Wallace, Alexander White, Kathy A Grako, Randal Lane, Allen Jo Cato, H Ralph Snodgrass
BACKGROUND AND AIMS: Neuropathic pain is a significant medical problem needing more effective treatments with fewer side effects. Overactive glutamatergic transmission via N-methyl-d-aspartate receptors (NMDARs) are known to play a role in central sensitization and neuropathic pain. Although ketamine, a NMDAR channel-blocking antagonist, is often used for neuropathic pain, its side-effect profile and abusive potential has prompted the search for a safer effective oral analgesic. A novel oral prodrug, AV-101 (l-4 chlorokynurenine), which, in the brain, is converted into one of the most potent and selective GlyB site antagonists of the NMDAR, has been demonstrated to be active in animal models of neuropathic pain...
October 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29196879/the-feasibility-of-physiologically-based-pharmacokinetic-modeling-in-forensic-medicine-illustrated-by-the-example-of-morphine
#4
Nadine Schaefer, Daniel Moj, Thorsten Lehr, Peter H Schmidt, Frank Ramsthaler
In forensic medicine, expert opinion is often required concerning dose and time of intake of a substance, especially in the context of fatal intoxications. In the present case, a 98-year-old man died 4 days after admission to a hospital due to a femur neck fracture following a domestic fall in his retirement home. As he had obtained high morphine doses in the context of palliative therapy and a confusion of his supplemental magnesium tablets with a diuretic by the care retirement home was suspected by the relatives, a comprehensive postmortem examination was performed...
March 2018: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29171155/interactions-of-2s-6s-2r-6r-hydroxynorketamine-a-secondary-metabolite-of-r-s-ketamine-with-morphine
#5
Tuomas O Lilius, Hanna Viisanen, Viljami Jokinen, Mikko Niemi, Eija A Kalso, Pekka V Rauhala
Ketamine and its primary metabolite norketamine attenuate morphine tolerance by antagonising N-methyl-D-aspartate (NMDA) receptors. Ketamine is extensively metabolised to several other metabolites. The major secondary metabolite (2S,6S;2R,6R)-hydroxynorketamine (6-hydroxynorketamine) is not an NMDA antagonist. However, it may modulate nociception through negative allosteric modulation of α7 nicotinic acetylcholine receptors. We studied whether 6-hydroxynorketamine could affect nociception or the effects of morphine in acute or chronic administration settings...
November 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29126076/a-rapid-and-sensitive-chiral-lc-ms-ms-method-for-the-determination-of-ketamine-and-norketamine-in-mouse-plasma-brain-and-cerebrospinal-fluid-applicable-to-the-stereoselective-pharmacokinetic-study-of-ketamine
#6
Hidetoh Toki, Takuya Ichikawa, Akiko Mizuno-Yasuhira, Jun-Ichi Yamaguchi
A novel method for the rapid and sensitive chiral determination of ketamine and norketamine in mouse plasma, brain and cerebrospinal fluid (CSF) was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This method reduces the required matrix volume, compared with a previously reported chiral assay method for ketamine and norketamine. The method involves the deproteinization of a small amount of biological matrix (corresponding to 5μL of plasma, 10mg of brain, or 2.5μL of CSF) using a water-miscible organic solvent containing (2)H4-norketamine as an internal standard, the direct injection of the organic supernatant into an LC-MS/MS system, chiral separation on a CHIRALPAK AS-3R column (4...
October 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29049110/evidence-for-the-efficacy-of-systemic-opioid-sparing-analgesics-in-pediatric-surgical-populations-a-systematic-review
#7
REVIEW
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
https://www.readbyqxmd.com/read/29030928/pharmacokinetics-of-s-ketamine-during-prolonged-sedation-at-the-pediatric-intensive-care-unit
#8
Robert B Flint, Carole N M Brouwer, Anne S C Kränzlin, Loraine Lie-A-Huen, Albert P Bos, Ron A A Mathôt
BACKGROUND: S-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AIMS: The aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18 years during long-term sedation. Twenty-five children (median age: 0.42 years, range: 0...
November 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28976571/ketamine-and-norketamine-stability-in-whole-blood-at-ambient-and-4%C3%A2-c-conditions
#9
Benjamin Duy Tran, Ganesh S Moorthy, Athena F Zuppa
A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood up to 120 h at room temperature and 4 °C...
October 4, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28918327/determination-of-ketamine-and-its-main-metabolites-by-liquid-chromatography-coupled-to-tandem-mass-spectrometry-in-pig-plasma-comparison-of-extraction-methods
#10
Cindy Ramiole, Benoit D'Hayer, Vincent Boudy, Josette Legagneux, Julien Fonsart, Pascal Houzé
A rapid, sensitive and specific liquid chromatography coupled to tandem mass spectrometry method was developed for the simultaneous quantification pig plasma of ketamine and its two principal metabolites, norketamine and dehydronorketamine. Three extraction procoles were assessed including acetonitrile precipitation, Oase™ microplate extraction, and liquid-liquid extraction. Oase™ microplate extraction induced no significant matrix effect, important signal/noise ratio and good recoveries, ranging from 82 to 87% for the considered compounds...
September 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28888484/prediction-of-human-efficacious-antidepressant-doses-using-the-mouse-forced-swim-test
#11
Eunice Yuen, Steven Swanson, Jeffrey M Witkin
The forced swim test (FST) is a commonly used preclinical animal behavioural model for prediction of antidepressant activity in humans. While the FST may qualitatively predict efficacy, less is known about the quantitative translation of FST data to human efficacious doses. Assessing quantitative translation allows better predictions of human efficacious doses and a higher chance of success in the drug development process. Dose-response and time-course FST experiments were carried out on mice using four marketed antidepressants (citalopram, desipramine, bupropion, desvenlafaxine) in addition to ketamine, all with varying mechanisms of action...
October 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28858450/ketamine-for-depression-5-potential-pharmacokinetic-and-pharmacodynamic-drug-interactions
#12
REVIEW
Chittaranjan Andrade
Ketamine, administered in subanesthetic doses, is gaining recognition as an off-label treatment for severe and even treatment-refractory depression. This article explores potential pharmacokinetic and pharmacodynamic drug interactions of relevance to the use of ketamine in depression. Sparse evidence suggests that ketamine will not induce clinically significant drug interactions except to the extent that these are predictable by its clinical actions. A small body of literature indicates that drugs that induce cytochrome P450 (CYP)2B6 and CYP3A4 will reduce exposure to ketamine and that drugs that inhibit these enzymes will increase exposure to ketamine...
July 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28856576/changes-in-transcranial-motor-evoked-potentials-during-hemorrhage-are-associated-with-increased-serum-propofol-concentrations
#13
Jeremy A Lieberman, John Feiner, Mark Rollins, Russ Lyon
Transcranial motor evoked potentials (TcMEPs) monitor the integrity of the spinal cord during spine surgery. Propofol-based anesthesia is favored in order to enhance TcMEP quality. During intraoperative hemorrhage, TcMEP amplitudes may be reduced. The serum concentration of propofol may increase during hemorrhage. No study has determined whether changes in TcMEPs due to hemorrhage are related to changes in propofol blood levels. We monitored TcMEPs, mean arterial pressure (MAP), and cardiac output (CO) and hemoglobin in pigs (n = 6) undergoing controlled progressive hemorrhage during a standardized anesthetic with infusions of propofol, ketamine, and fentanyl...
August 30, 2017: Journal of Clinical Monitoring and Computing
https://www.readbyqxmd.com/read/28724494/pharmacokinetics-of-a-novel-transdermal-fentanyl-solution-in-rhesus-macaques-macaca-mulatta
#14
Gregory W Salyards, Marie-Josee Lemoy, Heather K Knych, Ashley E Hill, Kari L Christe
Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has been developed as a long-acting, single-administration topical opioid and was reported to provide at least 4 d of effective plasma concentrations in beagles (Canis familiaris). To evaluate the pharmacokinetic profile of TFS in healthy adult rhesus macaques, we used a 2-period, 2-treatment crossover study of a single topical administration of 1...
July 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28550529/single-administration-of-hbk-15-a-triple-5-ht1a-5-ht7-and-5-ht3-receptor-antagonist-reverses-depressive-like-behaviors-in-mouse-model-of-depression-induced-by-corticosterone
#15
Karolina Pytka, Monika Głuch-Lutwin, Magdalena Kotańska, Anna Waszkielewicz, Agnieszka Kij, Maria Walczak
Studies suggest that the blockade of 5-HT1A, 5-HT7, and 5-HT3 receptor may increase the speed of antidepressant response. 1-[(2,6-Dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15), dual 5-HT1A and 5-HT7 antagonists, showed significant antidepressant- and anxiolytic-like properties in our previous tests in rodents. In this study, we aimed to investigate their antidepressant potential using mouse model of corticosterone-induced depression...
May 26, 2017: Molecular Neurobiology
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
#16
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...
June 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28492297/recent-antiseizure-medications-in-the-intensive-care-unit
#17
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 antiseizure 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...
August 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28339766/higher-bioavailability-of-doxycycline-in-broiler-chickens-with-a-novel-in-feed-pharmaceutical-formulation
#18
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...
August 1, 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
#19
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...
November 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
#20
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
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