Simulation of propofol anaesthesia for intracranial decompression using brain hypothermia treatment

<p>Abstract</p> <p>Background</p> <p>Although propofol is commonly used for general anaesthesia of normothermic patients in clinical practice, little information is available in the literature regarding the use of propofol anaesthesia for intracranial decompression using brain hypothermia treatment. A novel propofol anaesthesia scheme is proposed that should promote such clinical application and improve understanding of the principles of using propofol anaesthesia for hypothermic intracranial decompression.</p> <p>Methods</p> <p>Theoretical analysis was carried out using a previously-developed integrative model of the thermoregulatory, hemodynamic and pharmacokinetic subsystems. Propofol kinetics is described using a framework similar to that of this model and combined with the thermoregulation subsystem through the pharmacodynamic relationship between the blood propofol concentration and the thermoregulatory threshold. A propofol anaesthesia scheme for hypothermic intracranial decompression was simulated using the integrative model.</p> <p>Results</p> <p>Compared to the empirical anaesthesia scheme, the proposed anaesthesia scheme can reduce the required propofol dosage by more than 18%.</p> <p>Conclusion</p> <p>The integrative model of the thermoregulatory, hemodynamic and pharmacokinetic subsystems is effective in analyzing the use of propofol anaesthesia for hypothermic intracranial decompression. This propofol infusion scheme appears to be more appropriate for clinical application than the empirical one.</p

A mathematical model of brain glucose homeostasis

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In Silico Resources to Assist in the Development and Evaluation of Physiologically-Based Kinetic Models

Since their inception in pharmaceutical applications, physiologically-based kinetic (PBK) models are increasingly being used across a range of sectors, such as safety assessment of cosmetics, food additives, consumer goods, pesticides and other chemicals. Such models can be used to construct organ-level concentration-time profiles of xenobiotics. These models are essential in determining the overall internal exposure to a chemical and hence its ability to elicit a biological response. There are a multitude of in silico resources available to assist in the construction and evaluation of PBK models. An overview of these resources is presented herein, encompassing all attributes required for PBK modelling. These include predictive tools and databases for physico-chemical properties and absorption, distribution, metabolism and elimination (ADME) related properties. Data sources for existing PBK models, bespoke PBK software and generic software that can assist in model development are also identified. On-going efforts to harmonise approaches to PBK model construction, evaluation and reporting that would help increase the uptake and acceptance of these models are also discussed

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Illustration of proposed scheme for using propofol anaesthesia for hypothermic intracranial decompression: (a) hypothermic intracranial decompression, (b) brain temperature prediction, (c) concentration calculation, (d) propofol administration

<p><b>Copyright information:</b></p><p>Taken from "Simulation of propofol anaesthesia for intracranial decompression using brain hypothermia treatment"</p><p>http://www.tbiomed.com/content/4/1/46</p><p>Theoretical Biology & Medical Modelling 2007;4():46-46.</p><p>Published online 29 Nov 2007</p><p>PMCID:PMC2217543.</p><p></p> The propofol-threshold mechanism is a linear relationship between blood propofol concentration and thermoregulatory threshold

Response of (a) blood and (b) CSF propofol concentration to short-term infusion

<p><b>Copyright information:</b></p><p>Taken from "Simulation of propofol anaesthesia for intracranial decompression using brain hypothermia treatment"</p><p>http://www.tbiomed.com/content/4/1/46</p><p>Theoretical Biology & Medical Modelling 2007;4():46-46.</p><p>Published online 29 Nov 2007</p><p>PMCID:PMC2217543.</p><p></p> Results for pharmacokinetic part of integrative model are compared with clinical data [14]

A perspective on the current use of the phase distribution model for predicting milk‐to‐plasma drug concentration ratio

Abstract The phase distribution model, proposed by Atkinson and Begg in 1990, has been widely used for predicting breastmilk‐to‐plasma drug concentration ratio. However, misrepresentations of the equations have been noted in recent publications. In this perspective, we revisit the derivation of the equations and provide an R/Shiny interface for the model with a view to helping scientists in this field acquire in‐depth understanding of the theoretical background and implementation of the model