Background Previous studies have reported conflicting results concerning the influence of age and gender on pharmacokinetics pharmacodynamics fentanyl, alfentanil, sufentanil. The aim this study was to determine new short-acting opioid remifentanil. Methods Sixty-five healthy adults (38 men 27 women) ages 20 85 y received remifentanil by constant-rate infusion 1 8 micrograms.kg-1.min-1 for 4 min. Frequent arterial blood samples were drawn assayed concentration. electroencephalogram used as a...

Background Unresolved issues with propofol include whether the pharmacokinetics are linear dose, influenced by method of administration (bolus vs. infusion), or age. Recently, a new formulation emulsion, containing disodium edetate (EDTA), was introduced in United States. Addition EDTA found manufacturer to significantly reduce bacterial growth. This study investigated influences administration, infusion rate, patient covariates, and on propofol. Methods Twenty-four healthy volunteers aged...

Background The authors studied the influence of age on pharmacodynamics propofol, including characterization relation between plasma concentration and time course drug effect. Methods evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 in persons older than 65 yr) an infusion (25, 50, 100, 200 microg x kg(-1) min(-1)) new (containing EDTA) formulation propofol were given each two different study days. was determined frequent arterial samples. electroencephalogram (EEG)...

The pharmacokinetics and pharmacodynamics of remifentanil were studied in 65 healthy volunteers using the electroencephalogram (EEG) to measure opioid effect. In a companion article, authors developed complex population pharmacokinetic pharmacodynamic models that incorporated age lean body mass (LBM) as significant covariates characterized intersubject variability. present determined whether dosing should be adjusted according LBM, or these covariate effects overshadowed by interindividual...

Remifentanil (GI87084B) is a new short-acting opioid with unique ester structure. Metabolism of remifentanil by hydrolysis results in very rapid elimination. The aim this study was to characterize detail the pharmacokinetic profile healthy male volunteers.Ten adult volunteers received zero-order infusion at doses ranging from 1 8 micrograms.kg-1.min-1 for 20 min. Frequent arterial blood samples were drawn and analyzed gas chromatographic mass spectroscopy determine concentrations. raw data...

Fentanyl, alfentanil, and sufentanil have important pharmacokinetic pharmacodynamic differences. Selecting one of these opioid analgesics as an adjunct to general anesthesia requires appreciation the relationship between characteristics drugs onset recovery from drug effect. Using a pharmacokinetic-pharmacodynamic model, authors simulated decrease in plasma fentanyl, concentration after intravenous administration by either bolus injection, brief infusion, or prolonged infusion. The...

The pharmacokinetic and pharmacodynamic properties of propofol were studied in 50 surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by variable-rate infusion, 0-20 mg/min, intermittent supplemental boluses, 10-20 mg part general anesthetic technique that included nitrous oxide, meperidine, muscle relaxants. For majority the patients (n = 30), pharmacokinetics best described two-compartment model. mean total body clearance rate 2.09 +/- 0.65 1/min (mean SD),...

Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics remifentanil alfentanil in healthy, adult male volunteers.Ten volunteers received infusions on separate sessions using randomized, open-label crossover design. Arterial blood samples were analyzed determine drug concentrations. electroencephalogram employed as measure effect. characterized moment analysis, nonlinear mixed effects model...

The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability no response shaking shouting, laryngoscopy, Bispectral Index (BIS), electroencephalographic approximate entropy (AE).Twenty healthy volunteers received either or alone then concurrently with a fixed concentration propofol, respectively, via target-controlled infusion. Responses shouting laryngoscopy were assessed multiple times after allowing plasma effect site...

Fentanyl was administered intravenously and transdermally to eight surgical patients determine the systemic bioavailability rate of absorption drug. Serum fentanyl concentrations reached a plateau approximately 14 h after placement transdermal delivery system. This maintained until removal system at 24 h. The decline in serum had terminal half-life 17.0 +/- 2.3 (mean SD), considerably longer than elimination seen intravenous administration same (6.1 2.0 h). absorption, predicted be 100...

Click on the links below to access all ArticlePlus for this article.Please note that files may launch a viewer application outside of your web browser.DRUG interactions are basis anesthetic practice. For example, induction anesthesia consist intravenous administration benzodiazepine before induction, hypnotic achieve loss consciousness, and an opioid blunt response noxious stimulation. Similarly, often is maintained with combination (e.g. , propofol, isoflurane) analgesic fentanyl, nitrous...

Dexmedetomidine is an alpha 2 agonist with potential utility in clinical anesthesia for both its sedative and sympatholytic properties.The pharmacokinetics hemodynamic changes that occurred ten healthy male volunteers were determined after administration of dexmedetomidine micrograms/kg by intravenous or intramuscular route separate study sessions.The absorption profile dexmedetomidine, as deconvolution the observed concentrations against unit disposition function derived from data, was...

Accurate dosing of propofol in children requires accurate knowledge pharmacokinetics this population. Improvement pharmacokinetic accuracy may depend on the incorporation individual patient factors into model or use population approaches to estimating parameters. We investigated whether incorporating subject covariates (e.g., age, weight, and gender) improved accuracy. also a mixed-effects computer program NONMEM) beyond obtained with models estimated using two simple approaches.We studied...

Fentanyl was administered to 21 patients using a computer-controlled infusion pump (CCIP) based on pharmacokinetic model. Eleven of the were dosed according pharmacokinetics described by McClain and Hug, ten Scott Stanski. The authors measured difference between arterial fentanyl concentrations predicted CCIP for each parameter set. median absolute performance error (MDAPE) in Hug's parameters 61%, MDAPE Stanski's 33%. population these analyzed pooled data technique. this showed smaller...

Background The effects of anesthetic drugs on electroencephalograms (EEG) have been studied to develop the EEG as a measure depth. Bispectral analysis is new quantitative technique that measures consistency phase and power relationships returns single measure, bispectral index. purpose this study was compare performance index, version 1.1, with other spectral drug effect for three commonly used drugs. Methods waveforms from 31 adults receiving infusions alfentanil, propofol, or midazolam...

Background Target-controlled infusion (TCI) systems can control the concentration in plasma or at site of drug effect. A TCI system that targets effect should be able to accurately predict time course The authors tested this by comparing performance three algorithms: plasmacontrol versus two algorithms for effect-site TCI. Methods One-hundred twenty healthy women patients received propofol via 12-min a target 5.4 microg/ml. In all groups, concentrations were computed using pharmacokinetics...

To investigate dexmedetomidine in children, the authors performed an open-label study of pharmacokinetics and pharmacodynamics dexmedetomidine.Thirty-six children were assigned to three groups; 24 received 12 no drug. Three doses dexmedetomidine, 2, 4, 6 microg x kg h, infused for 10 min. Cardiorespiratory responses sedation recorded h. Plasma concentrations collected h analyzed. Pharmacokinetic variables determined using nonlinear mixed effects modeling (NONMEM program). analyzed.Thirty-six...

Background Several studies relating electroencephalogram parameter values to clinical endpoints using a single (mostly hypnotic) drug at relatively low levels of central nervous system depression (sedation) have been published. However, the usefulness derived from for anesthesia largely depends on its ability predict response stimuli different intensity or painfulness under combination hypnotic and an (opioid) analgesic. This study was designed evaluate predictive performance spectral edge...

THE bispectral index (BIS, Aspect Medical Systems, Framingham, MA) is a complex electroencephalographic (EEG) parameter that integrates several disparate descriptors of the EEG into single variable and correlates behavioral assessments sedation hypnosis. 1,2We report two cases in which failed to measure depth anesthesia but instead was electromyographic (EMG) activity. In first case paradoxically increased after increasing propofol concentration, correlating with EMG second administration...

Background Lidocaine may be useful in the treatment of neuropathic pain states. The authors hypothesized that lidocaine would reduce tactile allodynia observed a rat nerve injury model. In an effort to determine site drug action, effects after intravenous, intrathecal, and regional administration were compared. Methods Rats underwent ligation left fifth sixth lumbar spinal nerves. 50% thresholds (g) for hind paw withdrawal awake rats von Frey hairs documented before, during, intravenous at...

Background Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of in critically ill has not been described. The aim current study was characterize compare pharmacokinetics pharmacodynamics midazolam continuous intravenous infusions sedation ICU patients. Methods With Institutional Review Board approval, 24 consenting adult were given either or a double-blind fashion...

Abstract Background The pharmacokinetic profiles of sufentanil available in the literature are conflicting because methodologic differences. Length sampling and assay sensitivity key factors involved accurately estimating volumes distribution, clearances, elimination phase. unit disposition function increasing doses were investigated influence dose administered on linearity pharmacokinetics was assessed.