Pharmacokinetic Model Selection for Target Controlled Infusions of Propofol

Coetzee, J. F.; Glen, J. B.; Wium, Cherylynn Angela; Boshoff, L

doi:10.1097/00000542-199506000-00003

Cited by 238 publications

(56 citation statements)

References 28 publications

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“…Although no reference values have been reported for divergence or wobble, it has been suggested that the performance of a computer-assisted target-controlled infusion is acceptable for clinical use in patients if the bias is not greater than ±15–20 per cent and the inaccuracy is less than 30–40 per cent (Coetzee and others 1995, Swinhoe and others 1998, Van den Niewenhuyzen and others 2000, Egan 2003). Assessed on these criteria, the accuracy of the TCI device programmed with the final PK model can be considered appropriate for targeted delivery of propofol in healthy adult cats.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, during the later stages of anaesthesia, errors were not increased by subsequent passage of infusion time, as supported by the negative value of median divergence for the TCI-2 group. The usefulness of TCI lies in its potential ability to accurately maintain and to make proportional changes to blood drug concentrations (Coetzee and others 1995, Swinhoe and others 1998, Van den Niewenhuyzen and others 2000). Variability among individuals should always be expected, and titration of the target Cp to achieve the desired effect is essential in order to optimise intraoperative conditions and ensure the appropriate drug concentrations for rapid awakening.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target‐controlled infusion

et al. 2016

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The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective neutering of seven healthy cats, premedicated intramuscularly with 0.3 mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood samples were collected over 240 minutes, and propofol concentrations were measured via a validated high-performance liquid chromatography assay. Selected pharmacokinetic parameters, determined by a three-compartment open linear model, were entered into a computer-controlled infusion pump (target-controlled infusion-1 (TCI-1)). In a second step, TCI-1 was used to induce and maintain general anaesthesia in nine cats undergoing neutering. Predicted and measured plasma concentrations of propofol were compared at specific time points. In a third step, the pharmacokinetic parameters were modified according to the results from the use of TCI-1 and were evaluated again in six cats. For this TCI-2 group, the median values of median performance error and median absolute performance error were -1.85 per cent and 29.67 per cent, respectively, indicating that it performed adequately. Neither hypotension nor respiratory depression was observed during TCI-1 and TCI-2. Mean anaesthesia time and time to extubation in the TCI-2 group were 73.90 (±20.29) and 8.04 (±5.46) minutes, respectively.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target‐controlled infusion

et al. 2016

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“…Since the PBPK analysis (see below) is consistent with a value of about 0.022, this was the value that was assumed for standard values for freepl (freepl st ). The reported values for the normal human blood/plasma ratio (rblpl st ) vary from 1.1 to 1.3: [18,19,29,30] and a standard value of the blood/plasma ratio (rblpl st ) of 1.0 was assumed.…”

Section: Methodsmentioning

confidence: 99%

Human physiologically based pharmacokinetic model for propofol

Levitt

Schnider

2005

BMC Anesthesiol

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BackgroundPropofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol.MethodsPKQuest, a freely distributed software routine , was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1) the value of the propofol oil/water partition coefficient; 2) the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion.ResultsThe PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance) is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters). The average weighted residual error (WRE) of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model.ConclusionA PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a PBPK model is that it can be used to predict the changes in kinetics produced by variations in physiological parameters. As one example, the model simulation of the changes in pharmacokinetics for morbidly obese subjects is discussed.

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“…Several of these reports indicate that at low concentrations ω-3 PUFAs (10 to 100 μM) produce anticancer effects through the induction of apoptosis rather than via cytotoxicity. Propofol (2,6 diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today [18,19] and is nontoxic to humans at high levels (3 to 8 μg/ml; 20 to 50 μM) [20]. Propofol is a potent antioxidant [21-24] and has been shown to stimulate protein kinase C [25,26], inhibit calcium entry in muscle cells [27] and increase the calcium sensitivity of myofilaments in ventricular myocytes [28].…”

Section: Introductionmentioning

confidence: 99%

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

et al. 2005

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Introduction Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 µg/ml). Clinically relevant concentrations of propofol (3 to 8 µg/ml; 20 to 50 µM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA).

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Pharmacokinetic Model Selection for Target Controlled Infusions of Propofol

Cited by 238 publications

References 28 publications

Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target‐controlled infusion

Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target‐controlled infusion

Human physiologically based pharmacokinetic model for propofol

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

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