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.

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

2000 ◽  
Vol 44 (3) ◽  
pp. 147
Author(s):  
TOMIEI KAZAMA ◽  
KAZUYUKI IKEDA ◽  
KOJI MORITA ◽  
MUTSUHITO KIKURA ◽  
MATSUYUKI DOI ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bispectral Index ◽  
Younger Patients ◽  
Effect Site

A Pharmacodynamic Explanation for the Rapid Onset/Offset of Rapacuronium Bromide 

1999 ◽  
Vol 90 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Peter M. C. Wright ◽  
Ronald Brown ◽  
Marie Lau ◽  
Dennis M. Fisher
Keyword(s):  
Plasma Concentration ◽  
Time Course ◽  
Plasma Concentrations ◽  
Rapid Onset ◽  
Muscle Relaxants ◽  
Adductor Pollicis ◽  
Effect Compartment ◽  
Nondepolarizing Muscle Relaxants ◽  
Effect Site ◽  
The Hill

Background Nondepolarizing muscle relaxants differ in their time course at the laryngeal adductors and the adductor pollicis, a result of differences in equilibration delays between plasma and effect sites, the sensitivity of each muscle to the relaxant, and the steepness of the concentration-effect relation at each muscle (the Hill factor). To determine whether similar differences exist for rapacuronium, a muscle relaxant with rapid onset and offset, the authors determined its pharmacodynamic characteristics. Methods The twitch tensions of the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff positioned at the vocal cords) were measured in 10 volunteers who were anesthetized with propofoL Rapacuronium, 1.5 mg/kg, was given and blood samples were collected. A semiparametric effect compartment pharmacodynamic model was fit to values for rapacuronium plasma concentrations and twitch tension of the adductor pollicis and laryngeal adductors. Results Equilibration between the rapacuronium plasma concentration and both effect sites was rapid (typical values for the rate constant for equilibration between plasma and the effect site are 0.405 per min for the adductor pollicis and 0.630 per min for the laryngeal adductors) and was more rapid at the laryngeal adductors than at the adductor pollicis (ratio, 1.59+/-0.16; mean +/- SD). The steady state rapacuronium plasma concentration that depressed twitch tension by 50% and the Hill factor were similar for the two muscles. Conclusions The rapid onset and offset of rapacuronium can be explained by the rapid equilibration between concentrations in plasma and at the effect site. Unlike the finding for other nondepolarizing muscle relaxants, the laryngeal muscles are not resistant to rapacuronium.

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.

Patterns of Cerebral Blood Flow and Systemic Hemodynamics During Arithmetic Processing

2008 ◽  
Vol 22 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Natalie Werner ◽  
Neval Kapan ◽  
Gustavo A. Reyes del Paso
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Time Course ◽  
Doppler Sonography ◽  
Transcranial Doppler Sonography ◽  
Systemic Hemodynamics ◽  
Heart Period ◽  
Blood Flow Velocities ◽  
Flow Velocities

The present study explored modulations in cerebral blood flow and systemic hemodynamics during the execution of a mental calculation task in 41 healthy subjects. Time course and lateralization of blood flow velocities in the medial cerebral arteries of both hemispheres were assessed using functional transcranial Doppler sonography. Indices of systemic hemodynamics were obtained using continuous blood pressure recordings. Doppler sonography revealed a biphasic left dominant rise in cerebral blood flow velocities during task execution. Systemic blood pressure increased, whereas heart period, heart period variability, and baroreflex sensitivity declined. Blood pressure and heart period proved predictive of the magnitude of the cerebral blood flow response, particularly of its initial component. Various physiological mechanisms may be assumed to be involved in cardiovascular adjustment to cognitive demands. While specific contributions of the sympathetic and parasympathetic systems may account for the observed pattern of systemic hemodynamics, flow metabolism coupling, fast neurogenic vasodilation, and cerebral autoregulation may be involved in mediating cerebral blood flow modulations. Furthermore, during conditions of high cardiovascular reactivity, systemic hemodynamic changes exert a marked influence on cerebral blood perfusion.

Time course study of blood pressure in children over a three-year period. Bogalusa Heart Study

Hypertension ◽  
1980 ◽  
Vol 2 (4) ◽  
pp. 102-108 ◽  
Author(s):  
A. W. Voors ◽  
L. S. Webber ◽  
G. S. Berenson
Keyword(s):  
Blood Pressure ◽  
Time Course ◽  
Bogalusa Heart Study ◽  
Heart Study ◽  
Time Course Study

Time course of insulin resistance associated with feeding dogs a high-fat diet

1997 ◽  
Vol 272 (1) ◽  
pp. E147-E154 ◽  
Author(s):  
A. P. Rocchini ◽  
P. Marker ◽  
T. Cervenka
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Glucose Uptake ◽  
Dose Response ◽  
High Fat Diet ◽  
Time Course ◽  
Rapid Development ◽  
Diet Group ◽  
Whole Body ◽  
High Fat

The current study evaluated both the time course of insulin resistance associated with feeding dogs a high-fat diet and the relationship between the development of insulin resistance and the increase in blood pressure that also occurs. Twelve adult mongrel dogs were chronically instrumented and randomly assigned to either a control diet group (n = 4) or a high-fat diet group (n = 8). Insulin resistance was assessed by a weekly, single-dose (2 mU.kg-1.min-1) euglycemic-hyperinsulinemic clamp on all dogs. Feeding dogs a high-fat diet was associated with a 3.7 +/- 0.5 kg increase in body weight, a 20 +/- 4 mmHg increase in mean blood pressure, a reduction in insulin-mediated glucose uptake [(in mumol-kg-1.min-1) decreasing from 72 +/- 6 before to 49 +/- 7 at 1 wk, 29 +/- 3 at 3 wk, and 30 +/- 2 at 6 wk of the high-fat diet, P < 0.01]. and a reduced insulin-mediated increase in cardiac output. In eight dogs (4 high fat and 4 control), the dose-response relationship of insulin-induced glucose uptake also was studied. The whole body glucose uptake dose-response curve was shifted to the right, and the rate of maximal whole body glucose uptake was significantly decreased (P < 0.001). Finally, we observed a direct relationship between the high-fat diet-induced weekly increase in mean arterial pressure and the degree to which insulin resistance developed. In summary, the current study documents that feeding dogs a high-fat diet causes the rapid development of insulin resistance that is the result of both a reduced sensitivity and a reduced responsiveness to insulin.

scholarly journals Changing the Drug Delivery System: Does it Add to Non-Compliance Ramifications Control? A Simulation Study on the Pharmacokinetics and Pharmacodynamics of Atypical Antipsychotic Drug

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 297
Author(s):  
Mohammed H. Elkomy
Keyword(s):  
Monte Carlo ◽  
Plasma Concentration ◽  
Monte Carlo Simulations ◽  
Time Course ◽  
Rating Scale ◽  
Test Dose ◽  
Immediate Release ◽  
State Recovery ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale

This study investigates the pharmacokinetic (PK) and pharmacodynamic (PD) consequences of shifting from Quetiapine fumarate immediate-release (IR) to extended-release (XR) formulation in non-adherent schizophrenia patients. Monte-Carlo simulations using population PK and PD models were implemented to predict the time course of plasma concentration and Brief Psychiatric Rating Scale (BPRS) scores following the oral administration of 200 mg Seroquel® every 12 h and 400 mg Seroquel XR® every 24 h in patients experiencing dose delay, omission or doubling. Parameters were computed and their distributions were compared using the Kolmogorov–Smirnov test. Dose irregularities with both formulations had different effects on plasma concentration and %reduction in BPRS scores from baseline. However, the odds ratio of getting a %reduction in BPRS below 14%, or plasma concentration exceeding 500 µg/L, were comparable for adherent and non-adherent patients. Plasma therapeutic concentration after treatment cessation was maintained for <24 h in 48% and 29.6% of patients, and a steady state recovery time of <48 h was achieved in 51% and 13.4% of patients on the IR and XR formulations, respectively. Monte-Carlo simulations predict that the risks associated with the IR dose irregularities are not worsened when the XR formulation is used instead. Non-adherence events involving a single dose of either formulation do not require rescue doses.

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