keyword
https://read.qxmd.com/read/38536664/pharmacokinetics-of-subcutaneous-ketamine-administration-via-the-omnipod%C3%A2-system-in-dogs
#1
JOURNAL ARTICLE
Claudia Colón, Peter Early, Karen Muñana, Natasha Olby, Christopher Mariani, Shelby Mancini, Gilad Fefer, Zhong Li, Jessica Briley, Kate Bailey, Duncan Lascelles, Kristen Messenger
Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI...
March 27, 2024: Journal of Veterinary Pharmacology and Therapeutics
https://read.qxmd.com/read/38519818/stimulus-mediation-specificity-and-impact-of-menthol-in-rats-trained-to-discriminate-puffs-of-nicotine-e-cigarette-aerosol-from-nicotine-free-aerosol
#2
JOURNAL ARTICLE
Yasmin Alkhlaif, Keith L Shelton
RATIONALE: It is unclear if e-cigarettes have reduced abuse liability relative to traditional cigarettes, especially when considering advanced devices which deliver nicotine more efficiently. Translatable and predictive animal models are needed to addresses this question. OBJECTIVES: Our goal was to explore the subjective stimulus effects of e-cigarettes by training rats to discriminate puffs of nicotine aerosol from vehicle aerosol using an aerosol delivery system designed to model e-cigarette use patterns in humans...
March 23, 2024: Psychopharmacology
https://read.qxmd.com/read/38490790/ketamine-efficacy-for-management-of-status-epilepticus-considerations-for-prehospital-clinicians
#3
REVIEW
Nikhil C Williams, Lindsey A Morgan, Jonathan Friedman, Jeffrey Siegler
Current first-line therapies for seizure management recommend benzodiazepines, which target gamma-aminobutyric acid type A channels to stop the seizure activity. However, seizures may be refractory to traditional first-line therapies, transitioning into status epilepticus and becoming resistant to gamma-aminobutyric acid type A augmenting drugs. Although there are other antiseizure medications available for clinicians to use in the intensive care unit, these options can be less readily available outside of the intensive care unit and entirely absent in the prehospital setting...
2024: Air Medical Journal
https://read.qxmd.com/read/38283689/intramuscular-ketamine-vs-midazolam-for-rapid-risk-reduction-in-suicidal-depressed-emergency-patients-clinical-trial-design-and-rationale
#4
JOURNAL ARTICLE
Sumra Sajid, Ryan E Lawrence, Hanga C Galfalvy, John G Keilp, Vivek K Moitra, J John Mann, Michael F Grunebaum
Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED...
January 2024: Journal of affective disorders reports
https://read.qxmd.com/read/38177696/gm-1020-a-novel-orally-bioavailable-nmda-receptor-antagonist-with-rapid-and-robust-antidepressant-like-effects-at-well-tolerated-doses-in-rodents
#5
JOURNAL ARTICLE
Adam K Klein, Eric W Austin, Michael J Cunningham, Dino Dvorak, Silvia Gatti, Sarah K Hulls, Laszlo Kiss, Andrew C Kruegel, Gerard J Marek, Mariusz Papp, Jonathan Sporn, Zoë A Hughes
The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and a side effect profile that necessitates in-clinic dosing. GM-1020 is a novel NMDAR antagonist that was developed to address these limitations of ketamine as a treatment for depression. Here, we present the preclinical characterization of GM-1020 alongside ketamine, for comparison. In vitro, we profiled GM-1020 for binding to NMDAR and functional inhibition using patch-clamp electrophysiology...
January 4, 2024: Neuropsychopharmacology
https://read.qxmd.com/read/38162029/cerebrospinal-fluid-exploratory-proteomics-and-ketamine-metabolite-pharmacokinetics-in-human-volunteers-after-ketamine-infusion
#6
JOURNAL ARTICLE
Ruin Moaddel, Cristan A Farmer, Mani Yavi, Bashkim Kadriu, Min Zhu, Jinshui Fan, Qinghua Chen, Elin Lehrmann, Giovanna Fantoni, Supriyo De, Caio H Mazucanti, Elia E Acevedo-Diaz, Peixiong Yuan, Todd D Gould, Lawrence T Park, Josephine M Egan, Luigi Ferrucci, Carlos A Zarate
Ketamine is a treatment for both refractory depression and chronic pain syndromes. In order to explore ketamine's potential mechanism of action and whether ketamine or its metabolites cross the blood brain barrier, we examined the pharmacokinetics of ketamine and its metabolites-norketamine (NK), dehydronorketamine (DHNK), and hydroxynorketamines (HNKs)-in cerebrospinal fluid (CSF) and plasma, as well as in an exploratory proteomic analysis in the CSF of nine healthy volunteers who received ketamine intravenously (0...
December 15, 2023: IScience
https://read.qxmd.com/read/37979888/do-the-enantiomers-of-ketamine-bind-enantioselectively-to-human-serum-albumin
#7
JOURNAL ARTICLE
Sebastian Schmidt, Ulrike Holzgrabe
The binding of drugs to plasma proteins is an important process in the human body and has a significant influence on pharmacokinetic parameter. Human serum albumin (HSA) has the most important function as a transporter protein. The binding of ketamine to HSA has already been described in literature, but only of the racemate. The enantiomerically pure S-ketamine is used as injection solution for induction of anesthesia and has been approved by the Food and Drug Administration for the therapy of severe depression as a nasal spray in 2019...
November 17, 2023: European Journal of Pharmaceutical Sciences
https://read.qxmd.com/read/37920424/ketamine-in-trauma-a-literature-review-and-administration-guidelines
#8
REVIEW
Kristen Reede, Reid Bartholomew, Dana Nielsen, Mentor Ahmeti, Khaled Zreik
Ketamine is a phencyclidine (PCP) derivative, which primarily acts as a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine serves as an analgesic and a dissociative sedative that produces potent analgesia, sedation, and amnesia while preserving spontaneous respiratory drive. It is rapidly gaining acceptance in the management of pain as multiple studies have demonstrated its reliable efficacy and a wide margin of safety. This article reviews some of these studies, the history of ketamine, and its pharmacological and pharmacokinetic properties...
November 2023: Curēus
https://read.qxmd.com/read/37882811/oral-ketamine-may-offer-a-solution-to-the-ketamine-conundrum
#9
REVIEW
Megan Dutton, Adem T Can, Jim Lagopoulos, Daniel F Hermens
Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative...
December 2023: Psychopharmacology
https://read.qxmd.com/read/37805261/general-intravenous-anesthetics-pharmacodynamics-pharmacokinetics-and-chiral-properties
#10
JOURNAL ARTICLE
Ružena Čižmáriková, Ladislav Habala, Mário Markulia
In continuation of our published review on general inhalational anesthetics, the current article presents a survey of intravenous agents for general anaesthesia. From chemical point of view these compounds belong to structurally diverse categories, such as barbiturates - thiopental (Sodium pentothal®, Trapanal®, Pentothal®), methohexital (Brevital®), and hexobarbital (Evipan®, Hexenal®, Citopan®, Tobinal®); non-barbiturate derivatives - ketamine (Ketalar® Ketaset®), esketamine (Ketanest®), and etomidate (Amidate®, Hypnomidate®), phenolic derivatives - propofol (Diprivan®); steroid derivatives - mixture of alfadolone and alfaxalone (Althesin® in human and Saffan® in veterinary anesthesia); and derivatives of phenylacetic acid - propanidid (Epontol®, Sombrevin®)...
2023: Ceská a Slovenská Farmacie
https://read.qxmd.com/read/37783840/antidepressants-enter-cells-organelles-and-membranes
#11
REVIEW
Zack Blumenfeld, Kallol Bera, Eero Castrén, Henry A Lester
We begin by summarizing several examples of antidepressants whose therapeutic actions begin when they encounter their targets in the cytoplasm or in the lumen of an organelle. These actions contrast with the prevailing view that most neuropharmacological actions begin when drugs engage their therapeutic targets at extracellular binding sites of plasma membrane targets-ion channels, receptors, and transporters. We review the chemical, pharmacokinetic, and pharmacodynamic principles underlying the movements of drugs into subcellular compartments...
October 2, 2023: Neuropsychopharmacology
https://read.qxmd.com/read/37733945/influence-of-intravenous-s-ketamine-on-the-pharmacokinetics-of-oral-morphine-in-healthy-volunteers
#12
JOURNAL ARTICLE
Terhi J Lohela, Satu Poikola, Daniel Backmansson, Outi Lapatto-Reiniluoto, Janne T Backman, Klaus T Olkkola, Tuomas O Lilius
BACKGROUND: Subanesthetic ketamine may reduce perioperative consumption of opioids. We studied whether intravenous S-ketamine alters the pharmacokinetics of oral morphine in healthy volunteers. METHODS: In this paired, randomized, double-blind, crossover trial, 12 participants under a 2-hour intravenous S-ketamine (0.57 mg/kg/h) or placebo infusion received oral morphine (0.2 mg/kg) at 30 minutes. Plasma concentrations of ketamine, morphine, and their major metabolites were quantified for 24 hours...
September 21, 2023: Anesthesia and Analgesia
https://read.qxmd.com/read/37683228/pharmacokinetics-of-ketamine-transfer-into-human-milk
#13
JOURNAL ARTICLE
Elleana Majdinasab, Palika Datta, Kaytlin Krutsch, Teresa Baker, Thomas W Hale
PURPOSE/BACKGROUND: Ketamine is an N -methyl- d -aspartate-antagonistic dissociative anesthetic infused intermittently for off-label management of treatment-resistant depression, acute suicidality, and postpartum depression. Despite the prevalence of postpartum depression nearing upward of 15% of deliveries, almost no research has been done to evaluate its safety during lactation. METHODS: In this study, human milk samples were released from the InfantRisk Center's Human Milk Biorepository of 4 participants treated with intermittent ketamine infusions (49-378 mg) to determine the levels of the drug and its active norketamine metabolite using liquid chromatography-mass spectrometry...
September 2023: Journal of Clinical Psychopharmacology
https://read.qxmd.com/read/37679283/requirement-for-discharge-in-the-care-of-a-responsible-adult-in-procedural-sedation-in-the-emergency-department-necessity-or-potential-barrier-to-health-equity
#14
JOURNAL ARTICLE
Armon Ayandeh, Natalija Farrell, Alexander Y Sheng
BACKGROUND: Procedural sedation is commonly practiced by emergency physicians to facilitate patient care in the emergency department (ED). Although various guidelines have modernized our approach to procedural sedation, many procedural sedation guidelines and practices still often require that patients be discharged into the care of a responsible adult. DISCUSSION: Such requirement for discharge often cannot be met by underserved and undomiciled patients. Benzodiazepines, opioids, propofol, ketamine, "ketofol," etomidate, and methohexital have all been utilized for procedural sedation in the ED...
June 9, 2023: Journal of Emergency Medicine
https://read.qxmd.com/read/37670605/ketamine-use-in-adult-and-pediatric-patients-receiving-extracorporeal-membrane-oxygenation-ecmo-a-systematic-review
#15
REVIEW
Trenton Flanagan, Kevin Mercer, Peter N Johnson, Jamie Miller, Faeeq S Yousaf, Jordan A Fuller
Background: Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug interactions, the PK changes associated with ECMO make appropriate analgosedative selection challenging. Ketamine is less lipophilic and has lower protein binding than alternative agents, and may be less impacted by the PK changes during ECMO. Objective: To systematically identify all instances of ketamine use during ECMO support in the literature to elucidate associated efficacy and safety outcomes and prevalence of use, as well as commonly used dosing strategies and pharmacokinetic data...
September 6, 2023: Journal of Pharmacy Practice
https://read.qxmd.com/read/37594592/is-the-one-compartment-model-with-first-order-absorption-a-useful-approximation
#16
JOURNAL ARTICLE
Michael Weiss
PURPOSE: The one-compartment model with first order absorption (ka1C) has been extensively used to fit oral data. But when the disposition parameters of the drug are not available, the bias in the parameter estimates remains unclear. In this paper, the effect of potential misspecification of the area under the curve (AUC) and the mean absorption time (MAT) was evaluated for three relatively slowly absorbed drugs/formulations. METHODS: Assuming a three-compartment disposition model with an input (absorption) rate described as a sum of two inverse Gaussian functions (2IG3C) as the true model, the deviations of AUC and MAT estimated with simpler models were analyzed...
August 18, 2023: Pharmaceutical Research
https://read.qxmd.com/read/37551774/item-response-theory-in-early-phase-clinical-trials-utilization-of-a-reference-model-to-analyse-the-montgomery-%C3%A3-sberg-depression-rating-scale-madrs
#17
JOURNAL ARTICLE
Marije E Otto, Kirsten R Bergmann, Marieke L de Kam, Kasper Recourt, Gabriël E Jacobs, Michiel J van Esdonk
In clinical trials, Montgomery-Åsberg Depression Rating Scale (MADRS) questionnaire data is added up to total scores before analysis, assuming equal contribution of each separate question. Item Response Theory (IRT)-based analysis avoids this by using individual question responses to determine the latent variable (ψ), which represents a measure of depression severity. However, utilization of IRT in early phase trials remains difficult, because large datasets are needed to develop IRT models. Therefore, we aimed to evaluate the application and assumptions of a reference IRT model for analysis of an early phase trial...
August 8, 2023: CPT: Pharmacometrics & Systems Pharmacology
https://read.qxmd.com/read/37487837/a-shea-butter-based-ketamine-ointment-the-antidepressant-effects-of-transdermal-ketamine-in-rats
#18
JOURNAL ARTICLE
Merve Akan, Ivan Skorodumov, Marcus W Meinhardt, Resit Canbeyli, Gunes Unal
The delayed onset of monoaminergic antidepressants and disadvantages of traditional administration routes created the need for alternative non-invasive delivery methods with rapid onset therapeutic effect. Ketamine attracted attention as a fast-acting glutamatergic antidepressant with ideal physiochemical properties for alternative routes of administration. However, there is no sufficient data for its transdermal use in depression. In this proof-of-concept study, we investigated the antidepressant effects of transdermal ketamine delivered via a novel ointment with skin protective, emulsifying and permeation enhancing properties...
July 22, 2023: Behavioural Brain Research
https://read.qxmd.com/read/37376031/pharmacokinetic-and-biomarker-quantification-studies-on-vancomycin-loaded-pegylated-liposomes-and-its-potential-to-reduce-vancomycin-induced-kidney-injury-a-rat-study
#19
JOURNAL ARTICLE
Medha D Joshi, Paulina Iacoban, Marc H Scheetz
Vancomycin is a commonly used antibiotic in hospital settings, especially against Methicillin-resistant staphylococcus aureus (MRSA). One of the major adverse events of vancomycin use in adults is kidney injury. The drug concentration, specifically the area under the concentration curve, predicts kidney injury in adults receiving vancomycin. To attempt to reduce vancomycin-induced nephrotoxicity, we have successfully encapsulated vancomycin in polyethylene glycol-coated liposomes (PEG-VANCO-lipo). We have previously carried out in vitro cytotoxicity studies on kidney cells using PEG-VANCO-lipo and found it to be minimally toxic compared to the standard vancomycin...
May 24, 2023: Pharmaceutics
https://read.qxmd.com/read/37267048/the-clinical-toxicology-of-ketamine
#20
REVIEW
Leo J Schep, Robin J Slaughter, Martin Watts, Elliot Mackenzie, Paul Gee
INTRODUCTION: Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug. OBJECTIVES: To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity...
June 2023: Clinical Toxicology
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