pharmacokinetics, ketamine

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...

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...

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...

We investigated the effect of isoflurane and ketamine-xylazine anesthesia on the positron emission tomography (PET) tracer [18 F]SynVesT-1 in the mouse brain. [18 F]SynVesT-1 PET scans were performed in C57BL/6J mice in five conditions: isoflurane anesthesia (ANISO), ketamine-xylazine (ANKX), awake freely moving (AW), awake followed by isoflurane administration (AW/ANISO) or followed by ketamine-xylazine (AW/ANKX) 20 min post tracer injection. ANISO, ANKX and AW scans were also performed in mice administered with levetiracetam (LEV, 200 mg/kg) to assess non-displaceable binding...

The extent and rate of bioavailability are fundamental measures to characterize the pharmacokinetics of drugs after oral administration. Together with bioavailability (F), the mean absorption time (MAT) can be used to define the rate of bioavailability, i.e., the rate of drug absorption. Previous results suggest that F may depend on MAT. Estimates of F and MAT were obtained from the input function (sum of two inverse Gaussian functions) used to model the oral absorption process. The estimation was performed by population analysis (nonlinear mixed-effects modeling) based on data from bioavailability studies in healthy volunteers...

Major depressive disorder is a common psychiatric disorder, with ∼30% of patients suffering from treatment-resistant depression. Based on preclinical studies on ketamine, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) activation may be a promising therapeutic approach. In this study, we synthesized a series of novel 3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide analogs and analyzed their potential as AMPAR potentiators. Compounds 5aa and 7k exhibited high potentiation with little agonist activity in a high-throughput screen using a calcium influx assay in cultured hippocampal primary neurons...

AIM: We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children. MATERIALS & METHODS: A previously developed population pharmacokinetic model was used to simulate exposures and evaluate target attainment, as well as the association with oxygen desaturation in children ≤17 years treated with intravenous ketamine. RESULTS: In 2022 children, there was no significant association between simulated plasma ketamine concentrations and oxygen saturation; however, a higher cumulative area under the curve was associated with increased odds of progression to significant desaturation (<85%), though magnitude of effect was small...

The purpose of this study was to investigate the effects of volatile anesthetic agents isoflurane and sevoflurane, at clinically relevant concentrations, on the fluidity of lipid membranes and permeability of the blood-brain barrier (BBB). We analyzed the in vitro effects of isoflurane or ketamine using erythrocyte ghosts (sodium fluorescein permeability) monolayers of brain microvascular endothelial cells ([13 C]sucrose and fluorescein permeability), or liposomes (fluorescence anisotropy). Additionally, we determined the effects of 30-min exposure of mice to isoflurane on the brain tight junction proteins...

BACKGROUND AND OBJECTIVES: Understanding the processes that determine the time course of drug absorption rates is of great interest. This study aims to answer the questions: (1) How well can the in vitro dissolution rate predict the in vivo input function (absorption rate) of a prolonged-release ketamine dosage form (PR-ketamine)? (2) Is the information obtained from the in vitro dissolution rate profile useful in estimating bioavailability? METHODS: In vivo plasma concentration data were obtained from 15 healthy volunteers after intravenous and oral dosing of 20 mg PR-ketamine tablets...

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support...

We present the rationale for testing ketamine as an add-on therapy for treating benzodiazepine refractory (established) status epilepticus. In animal studies, ketamine terminates benzodiazepine refractory status epilepticus by interfering with the pathophysiological mechanisms and is a neuroprotectant. Ketamine does not suppress respiration when used for sedation and anesthesia. A Series of reports suggest that ketamine can help terminate refractory and super refractory status epilepticus. We propose to use 1 or 3 mg/Kg ketamine intravenously based on animal-to-human conversion and pharmacokinetic studies...

Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required...

Since the 2000s, an increasing number of new psychoactive substances (NPS) have appeared on the drug market. Arylcyclohexylamine (ACH) compounds such as ketamine, phencyclidine and eticyclidine derivatives are of particular concern, given their rapidly increasing use and the absence of detailed toxicity data. First used mainly for their pharmacological properties in anesthesia, their recreational use is increasing. ACH derivatives have an antagonistic activity against the N-methyl-D-aspartate receptor, which leads to dissociative effects (dissociation of body and mind)...

A convenient LC-MS/MS assay method to simultaneously and sensitively determine (R,S)-ketamine (Ket), (R,S)-norketamine (NK), and (2R,6R;2S,6S)-hydroxynorketamine (HNK) enantiomers in plasma and brain from mice was developed. This method enables the chiral separations of these six enantiomers in one analysis by constructing a column-switching system composed of one achiral column and two chiral columns with a relatively short analysis time (17 min). The chromatography involves the separation of (2R,6R;2S,6S)-HNK from (R,S)-Ket and (R,S)-NK on an octadecyl-silica column, followed by chiral separations on a CHIRALPAK AY-RH column for (2R,6R;2S,6S)-HNK or on a CHIRALPAK AS-RH column for the other analytes...

Perioperative pain management impacts patient morbidity, quality of life, and hospitalization cost. In children, it impacts not only the child, but the whole family. Adjuncts for improved perioperative analgesia continue to be sought to minimize adverse side effects associated with opioids and for those in whom regional or neuraxial anesthesia is not suitable. The use of ketamine and alpha agonists may be useful in these settings but have noted adverse effects including hallucinations, hemodynamic instability, and excessive sedation...

OBJECTIVE: To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. STUDY DESIGN: Nonrandomized crossover. ANIMALS: Six adult, Thoroughbred horses. METHODS: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively...

BACKGROUND: Abnormal peripheral perfusion and postinduction hypotension are associated with postoperative adverse outcomes. S-ketamine may stimulate blood circulation by activating the sympathetic nervous system. This study aimed to identify whether S-ketamine may improve the hemodynamic profile, relative to saline. METHODS: 115 patients were assessed for eligibility for participation in this study. A total of 100 patients were included. The patients (n=50 for each group) were randomly allocated to the Test group, treated with S-ketamine plus propofol, cisatracurium and sufentanil, and to the Control group, treated with saline plus propofol, cisatracurium, and sufentanil...

Introduction: we sought to explore the efficacy of ketamine in a patient on extracorporeal membrane oxygenation (ECMO) receiving ketamine for sedation by investigating the utility of plasma ketamine concentrations. Case report: retrospective chart review of one critically ill patient on ECMO Discussion: This was a descriptive review of serial plasma ketamine concentrations in an ECMO patient. Although no reference plasma concentrations exist in ECMO patients, ketamine levels appeared to be lower than those seen in surgical patients not on ECMO...

The ability to combine and use drugs in a single infusion device may be useful in resource-limited settings. This study examined the chemical stability of an opioid-sparing mixture of ketamine, lidocaine and magnesium sulphate when combined in a single syringe. High-performance liquid chromatography and atomic absorption spectrophotometry were performed on six syringes containing the three-drug mixture. Since most opioid-sparing techniques typically rely on a 24-hour infusion regime, we tested stability at the initial admixing and 24 hours later...

Ketamine is administered predominantly via the intravenous route for the various indications, including anesthesia, pain relief and treatment of depression. Here we report on the pharmacokinetics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S -ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two oral thin films on separate occasions in a randomized crossover design. The oral thin films were placed sublingually ( n = 15) or buccally ( n = 5) and left to dissolve for 10 min in the mouth during which the subjects were not allowed to swallow...