scholarly journals Assessment of the clinical validity of an adjusted Marsh pharmacokinetic model using an effect-site rate constant (ke0) of 1.21 min-1

2021 ◽  
Vol 27 (2) ◽  
pp. 83-91
Author(s):  
J.F. Coetzee ◽  
A. Links ◽  
A.I. Levin
Keyword(s):  
Rate Constant ◽  
Pharmacokinetic Model ◽  
Clinical Validity ◽  
Effect Site

Induction of general anaesthesia by effect-site target-controlled infusion of propofol: influence of pharmacokinetic model and ke0value

Anaesthesia ◽  
2014 ◽  
Vol 69 (5) ◽  
pp. 429-435 ◽  
Author(s):  
A. J. Thomson ◽  
G. Morrison ◽  
E. Thomson ◽  
C. Beattie ◽  
A. F. Nimmo ◽  
...  
Keyword(s):  
General Anaesthesia ◽  
Pharmacokinetic Model ◽  
Effect Site ◽  
Target Controlled Infusion

scholarly journals Early Phase Pharmacokinetics but Not Pharmacodynamics Are Influenced by Propofol Infusion Rate

2009 ◽  
Vol 111 (4) ◽  
pp. 805-817 ◽  
Author(s):  
Kenichi Masui ◽  
Marimo Kira ◽  
Tomiei Kazama ◽  
Satoshi Hagihira ◽  
Eric P. Mortier ◽  
...  
Keyword(s):  
Dose Rate ◽  
Rate Constant ◽  
Early Phase ◽  
Infusion Rate ◽  
Pharmacokinetic Model ◽  
Drug Effect ◽  
Lag Time ◽  
Time Shift ◽  
Pharmacokinetic Models ◽  
Arterial Blood

Background Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model. Methods Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure. Results Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate. Conclusions This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.

scholarly journals Titration of the plasma effect site equilibrium rate constant of propofol; a link method of 'Concentration-Probability-Time'

2010 ◽  
Vol 58 (3) ◽  
pp. 231
Author(s):  
Jong-Yeop Kim ◽  
Sung-Yong Park ◽  
Sun-Kyung Park ◽  
Jin-Soo Kim ◽  
Sang-Kee Min
Keyword(s):  
Rate Constant ◽  
Effect Site ◽  
Concentration Probability ◽  
Plasma Effect

Estimation of the Plasma Effect Site Equilibration Rate Constant (ke0) of Propofol in Children Using the Time to Peak Effect

2004 ◽  
Vol 101 (6) ◽  
pp. 1269-1274 ◽  
Author(s):  
Hernán R. Muñoz ◽  
Luis I. Cortínez ◽  
Mauricio E. Ibacache ◽  
Fernando R. Altermatt
Keyword(s):  
Rate Constant ◽  
Peak Effect ◽  
Auditory Evoked Potential ◽  
Pharmacokinetic Parameters ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Target Effect ◽  
Equilibration Rate ◽  
Plasma Effect

Background Targeting the effect site concentration may offer advantages over the traditional forms of administrating intravenous anesthetics. Because the lack of the plasma effect site equilibration rate constant (ke0) for propofol in children precludes the use of this technique in this population, the authors estimated the value of ke0 for propofol in children using the time to peak effect (tpeak) method and two pharmacokinetic models of propofol for children. Methods : The tpeak after a submaximal bolus dose of propofol was measured by means of the Alaris A-Line auditory evoked potential monitor (Danmeter A/S, Odense, Denmark) in 25 children (aged 3-11 yr) and 25 adults (aged 35-48 yr). Using tpeak and two previously validated sets of pharmacokinetic parameters for propofol in children, Kataria's and that used in the Paedfusor (Graseby Medical Ltd., Hertfordshire, United Kingdom), the ke0 was estimated according to a method recently published. Results The mean tpeak was 80 +/- 20 s in adults and 132 +/- 49 s in children (P < 0.001). The median ke0 in children was 0.41 min(-1) with the model of Kataria and 0.91 min(-1) with the Paedfusor model (P < 0.01). The corresponding t1/2 ke0 values, in minutes, were 1.7 and 0.8, respectively (P < 0.01). Conclusions : Children have a significantly longer tpeak of propofol than adults. The values of ke0 of propofol calculated for children depend on the pharmacokinetic model used and also can only be used with the appropriate set of pharmacokinetic parameters to target effect site in this population.

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