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The current opioid overdose crisis is being exacerbated by illicitly manufactured fentanyl and its analogs. Carfentanil is a fentanyl analog that is 10,000-times more potent than morphine, but limited information is available about its pharmacology. The present study had two aims: 1) to validate a method for quantifying carfentanil and its metabolite norcarfentanil in small-volume samples, and 2) to use the method for examining pharmacodynamic-pharmacokinetic relationships in rats. The analytical method involved liquid-liquid extraction of plasma samples followed by quantitation of carfentanil and norcarfentanil using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The method was validated following SWGTOX guidelines, and both analytes displayed limits of detection and quantification at 7.5 and 15 pg/mL, respectively. Male Sprague-Dawley rats fitted with jugular catheters and temperature transponders received subcutaneous carfentanil (1, 3 and 10 μg/kg) or saline. Repeated blood specimens were obtained over 8 h, along with pharmacodynamic measures including core temperature and catalepsy scores. Carfentanil produced dose-related hypothermia and catalepsy that lasted up to 8 h. Carfentanil C occurred at 15 min whereas metabolite C was at 1-2 h. Concentrations of both analytes increased in a dose-related fashion, but area-under-the-curve values were much greater than predicted after 10 μg/kg. Plasma half-life for carfentanil increased at higher doses. Our findings reveal that carfentanil produces marked hypothermia and catalepsy, which is accompanied by nonlinear accumulation of the drug at high doses. We hypothesize that impaired clearance of carfentanil in humans could contribute to life-threatening effects of this ultrapotent opioid agonist.
This article was published in the following journal.
Since 2013, opioid-related deaths have increased in Miami-Dade County, FL due to fentanyl and fentanyl analogs in the local heroin supply. From 2014 to 2015, a near 600% increase in fentanyl and fenta...
Fentanyl, and the numerous drugs derived from it, are contributing to the opioid overdose epidemic currently underway in the USA. To identify human exposure to these growing public health threats, an ...
To describe and analyze the involvement of fentanyl and fentanyl analogs (FAs) in drug-related deaths in West Virginia (WV), United States.
In the article entitled: "Carfentanil: a narrative review of its pharmacology and public health concerns" published online and in the April 2019 issue of the Journal, Can J Anesth 2019; DOI: https://d...
North America is experiencing an opioid overdose epidemic, fuelled by the proliferation of fentanyl, related analogues, and fentanyl-adulterated opioids. British Columbia, Canada has similarly experie...
This research is studying a new investigative imaging instrument called a nonlinear microscope (NLM). A nonlinear microscope can produce images similar to an ordinary pathologist's microsc...
Purpose: To compare the pain level and quality of life of the two sedation regimens consisting of diazepam in combination with meperidine or fentanyl. Materials and methods: A total of 40...
Evaluate the ability to image oral mucosa in healthy volunteer by nonlinear microscopy
The Phase I clinical trial in approximately 50 healthy volunteers will be conducted at a single clinical center in two stages. Stage 1 is an open-label, cross-over comparison of a single d...
For this study the investigators are looking to do the following: 1. To characterize human lung lesions by nonlinear microscopy using ex vivo tissues. 2. To establish the first spect...
A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)
Microscopic imaging techniques that utilize nonlinear responses of light-matter interactions which occur with high-intensity illumination, such as from LASERS, and specialized light signal detection instrumentation to produce images without the need for dyes or fluorescent labels.
The study of systems which respond disproportionately (nonlinearly) to initial conditions or perturbing stimuli. Nonlinear systems may exhibit "chaos" which is classically characterized as sensitive dependence on initial conditions. Chaotic systems, while distinguished from more ordered periodic systems, are not random. When their behavior over time is appropriately displayed (in "phase space"), constraints are evident which are described by "strange attractors". Phase space representations of chaotic systems, or strange attractors, usually reveal fractal (FRACTALS) self-similarity across time scales. Natural, including biological, systems often display nonlinear dynamics and chaos.
A preconceived judgment made without adequate evidence and not easily alterable by presentation of contrary evidence.
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Multiple Sclerosis MS
Multiple sclerosis (MS) is the most common disabling neurological condition affecting 100,000 young adults in the UK. The condition results from autoimmune damage to myelin, causing interference in nerve signaling. Symptoms experienced depend on the pa...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...