scholarly journals Influence of Administration Rate on Propofol Plasma–Effect Site Equilibration

2007 ◽  
Vol 107 (3) ◽  
pp. 386-396 ◽  
Author(s):  
Michel M. R. F. Struys ◽  
Marc J. Coppens ◽  
Nikolaas De Neve ◽  
Eric P. Mortier ◽  
Anthony G. Doufas ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Bispectral Index ◽  
Bolus Injection ◽  
Drug Effect ◽  
Compartment Model ◽  
Pharmacokinetic Models ◽  
Rapid Infusion ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Plasma Effect

Background The authors hypothesized a difference in plasma-effect site equilibration, depicted by a first-order constant k(e0), depending on the injection rate of propofol. Methods Sixty-one patients received 2.5 mg/kg propofol given as a bolus or as a 1-, 2-, or 3-min infusion. The Bispectral Index was used to monitor drug effect. Propofol predicted plasma concentration was calculated using a three-compartment model and the effect site concentration over time as the convolution between the predicted plasma concentration and the disposition function of the effect site concentration. The authors evaluated the influence of the infusion rate on the k(e0) by comparing the model with one k(e0) for all groups with models estimating different k(e0) values for each group. The authors also assessed the accuracy of two pharmacokinetic models after bolus injection. Results The best model based was a fixed (Bispectral Index > or = 90) plus sigmoidal model (Bispectral Index < 90) with two values of k(e0), one for the bolus (t(1/2) k(e0) = 1.2 min) and one for the infusions (t(1/2) k(e0) = 2.2 min). However, the tested pharmacokinetic models poorly predicted the arterial concentrations in the first minutes after bolus injection. Simulations showed the requirement for two k(e0) values for bolus and infusion was mostly a compensation for the inaccurate prediction of arterial concentrations after a bolus. Conclusion Propofol plasma-effect site equilibration occurs more rapidly after a bolus than after rapid infusion, based on the electroencephalogram as a drug effect measure, mostly because of misspecification of the pharmacokinetic model in the first minutes after bolus.

Comparison of Plasma Compartment versus  Two Methods for Effect Compartment–controlled Target-controlled Infusion for Propofol

2000 ◽  
Vol 92 (2) ◽  
pp. 399-399 ◽  
Author(s):  
Michel M. R. F. Struys ◽  
Tom De Smet ◽  
Birgit Depoorter ◽  
Linda F. M. Versichelen ◽  
Eric P. Mortier ◽  
...  
Keyword(s):  
Time Course ◽  
Drug Effect ◽  
Peak Effect ◽  
Effect Compartment ◽  
Loss Of Consciousness ◽  
Group Iii ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Plasma Effect

Background Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI. Methods One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured. Results The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II. Conclusion Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.

scholarly journals Induction Speed Is Not a Determinant of Propofol Pharmacodynamics

2004 ◽  
Vol 101 (5) ◽  
pp. 1112-1121 ◽  
Author(s):  
Anthony G. Doufas ◽  
Maryam Bakhshandeh ◽  
Andrew R. Bjorksten ◽  
Steven L. Shafer ◽  
Daniel I. Sessler
Keyword(s):  
Drug Effect ◽  
Peak Effect ◽  
Population Based ◽  
Pharmacodynamic Modeling ◽  
Time To Peak ◽  
Effect Site ◽  
Rate Of Increase ◽  
Effect Site Concentration ◽  
The Times ◽  
Plasma Effect

Background Evidence suggests that the rate at which intravenous anesthetics are infused may influence their plasma-effect site equilibration. The authors used five different rates of propofol administration to test the hypothesis that different sedation endpoints occur at the same effect site propofol concentration, independent of the infusion rate. The authors concurrently evaluated the automated responsiveness monitor (ARM) against other sedation measures and the propofol effect site concentration. Methods With Human Studies Committee approval, 18 healthy volunteers received five consecutive target-controlled propofol infusions. During each infusion, the effect site concentration was increased by a rate of 0.1, 0.3, 0.5, 0.7, or 0.9 microg . ml . min. The Bispectral Index and ARM were recorded at frequent intervals. The times of syringe drop and loss and recovery of responsiveness were noted. Pharmacokinetic and pharmacodynamic modeling was performed using NONMEM. Results When the correct rate of plasma-effect site equilibration was determined for each individual (plasma-effect site equilibration = 0.17 min, time to peak effect = 2.7 min), the effect site concentrations associated with each clinical measure were not affected by the rate of increase of effect site propofol concentration. ARM correlated with all clinical measures of drug effect. Subjects invariably stopped responding to ARM at lower effect site propofol concentrations than those associated with loss of responsiveness. Conclusions : Population-based pharmacokinetics, combined with real-time electroencephalographic measures of drug effect, may provide a means to individualize pharmacodynamic modeling during target-controlled drug delivery. ARM seems useful as an automated measure of sedation and may provide the basis for automated monitoring and titration of sedation for a propofol delivery system.

The Influence of Age on Propofol Pharmacodynamics

1999 ◽  
Vol 90 (6) ◽  
pp. 1502-1516. ◽  
Author(s):  
Thomas W. Schnider ◽  
Charles F. Minto ◽  
Steven L. Shafer ◽  
Pedro L. Gambus ◽  
Corina Andresen ◽  
...  
Keyword(s):  
Rate Constant ◽  
Canonical Correlation ◽  
Drug Effect ◽  
Peak Effect ◽  
Pharmacodynamic Model ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Equilibration Rate ◽  
Plasma Effect

Background The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. Methods The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. Results Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. Conclusions Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.

Comparison of the Effect-site keOs of Propofol for Blood Pressure and EEG Bispectral Index in Elderly and Younger Patients

1999 ◽  
Vol 90 (6) ◽  
pp. 1517-1527. ◽  
Author(s):  
Tomiei Kazama ◽  
Kazuyuki Ikeda ◽  
Koji Morita ◽  
Mutsuhito Kikura ◽  
Matsuyuki Doi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Bispectral Index ◽  
Time Course ◽  
Drug Infusion ◽  
Time Data ◽  
Aged Patients ◽  
Younger Patients ◽  
Spectral Edge Frequency ◽  
Effect Site

Background Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. Methods A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. Results The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients. Conclusions The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

Performance of the ARX-derived Auditory Evoked Potential Index as an Indicator of Anesthetic Depth

2002 ◽  
Vol 96 (4) ◽  
pp. 803-816 ◽  
Author(s):  
Michel M. R. F. Struys ◽  
Erik Weber Jensen ◽  
Warren Smith ◽  
N. Ty Smith ◽  
Ira Rampil ◽  
...  
Keyword(s):  
Bispectral Index ◽  
Evoked Potential ◽  
Auditory Evoked Potential ◽  
Noxious Stimulus ◽  
Gynecologic Surgery ◽  
Effect Compartment ◽  
Loss Of Consciousness ◽  
Anesthetic Depth ◽  
Effect Site ◽  
Effect Site Concentration

Background Autoregressive modeling with exogenous input of middle-latency auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed for monitoring anesthetic depth. The aim of the current study was to compare the accuracy of this new index with the Bispectral Index (BIS), predicted effect-site concentration of propofol, and hemodynamic measures. Methods Twenty female patients scheduled for ambulatory gynecologic surgery received effect compartment controlled infusion of propofol. Target effect-site concentration was started at 1.5 microg/ml and increased every 4 min by 0.5 microg/ml. At every step, sedation level was compared with monitoring values using different clinical scoring systems and reaction to noxious stimulus. Results Bispectral Index, AAI, and predicted propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness. Hemodynamic variables were poor indicators of the hypnotic-anesthetic status of the patient. BIS correlated best with propofol effect-site concentration, followed by AAI. Hemodynamic measurements did not correlate well. No indicators predicted reaction to noxious stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal. This reaction occurred more rapidly with the AAI than with BIS. Conclusion Bispectral Index, AAI, and predicted propofol effect-site concentration revealed information on the level of sedation and loss of consciousness but did not predict response to noxious stimulus.

scholarly journals Changes of Hemodynamics and Bispectral Index by Tracheal Intubation according to Effect-site Concentration of Remifentanil during Propofol Anesthesia

2007 ◽  
Vol 53 (5) ◽  
pp. 565 ◽  
Author(s):  
Hong Sik Lee ◽  
Jang-Ho Song ◽  
Helen Ki Shinn ◽  
Jeong Uk Han ◽  
Jong-Kwon Jung ◽  
...  
Keyword(s):  
Tracheal Intubation ◽  
Bispectral Index ◽  
Effect Site ◽  
Effect Site Concentration

scholarly journals Pharmacokinetics of Ciprofloxacin in Broiler Chickens After Single Intravenous and Intraingluvial Administration

2017 ◽  
Vol 40 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Sofiya Ivanova ◽  
Dimitrichka Dimitrova ◽  
Metodi Petrichev
Keyword(s):  
Body Weight ◽  
Plasma Concentration ◽  
Infectious Diseases ◽  
Crossover Study ◽  
Intravenous Injection ◽  
Broiler Chickens ◽  
Bolus Injection ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Pharmacokinetic Models

Abstract The trial was performed on 10 clinically healthy Ross hybrid chickens, 5 from each gender, weighing 2.75-2.84 kg. The tested quinolone was applied at the same dose for both routes of application - 10 mg/kg of body weight. Ciprofloxacin hydrochloridum 5% solution for i.v. and 1% solution for intraingluvial treatment were prepared. In a crossover study design, ciprofloxacin hydrochloridum was administered as 5 % solution for i.v. bolus injection to broiler chickens and after 14 days as 1 % solution for intraingluvial administration into a crop to the same birds. Serum ciprofloxacin concentrations were assayed by HPLC with UV detection at a wavelength of 279 nm. After intravenous injection the following pharmacokinetic parameters were determined: t1/2β = 9.07 h; t1/2α= 0.36 h; MRT = 10.20 h and MRT = 10.75 h; AUC0→∞ = 19.560 μg.h/mL and AUC0→∞ = 19.843 μg.h/mL. After intraingluvial application parameters determined by the two pharmacokinetic models were as: t1/2α= 0.86 h; t1/2β = 7,20 h and t1/2β = 7.89 h; MRT = 12.67 h and MRT = 12.93 h; AUC0→∞ = 11.340 μg.h/mL and AUC0→24 h = 11.973 μg.h/mL; Cmax = 2.841 μg/mL and Cmax = 2.638 μg/mL; Tmax = 0.48 h and Tmax = 0.39 h; t1/2abs. = 0.146 h; MAT = 2.47 h and MAT = 2.18 h; F = 57.91% and F = 63.89%. These results suggested that a dose of 10 mg/kg of body weight provides maximum plasma concentration ater intraingluvial administration and is effective in the control of many infectious diseases of poultry.

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