The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
J.r. Jacobs - One of the best experts on this subject based on the ideXlab platform.
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Algorithm to control "effect compartment" drug concentrations in Pharmacokinetic Model-driven drug delivery
IEEE Transactions on Biomedical Engineering, 1993Co-Authors: J.r. Jacobs, E.a. WilliamsAbstract:In most computer-controlled Pharmacokinetic Model-driven drug infusion pumps, simulation of a linear compartmental Pharmacokinetic Model is used to compute the rate of intravenous drug infusion required to achieve setpoint central compartment (plasma) drug concentrations. For many drugs, it has been suggested that it is the drug concentration in a hypothetical "effect" compartment, rather than in the plasma, that should be manipulated to achieve maximum control over pharmacologic action. Controlling the effect compartment drug concentration is algorithmically more difficult than controlling the central compartment drug concentration because of the time delay between administration of drug into the central compartment and its subsequent appearance in the effect compartment. The authors present a Model-based dosing algorithm for use in Pharmacokinetic Model-driven drug infusion devices that target the theoretical effect compartment drug concentration.
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Sources Of Error In Pharmacokinetic Model-driven Intravenous Drug Delivery
[1990] Proceedings of the Twelfth Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1990Co-Authors: J.r. JacobsAbstract:Computerized Pharmacokinetic Model-driven infusion devices are being investigated as a means of improving the efficiency of intravenous administration of some drugs. Agreement between Model-predicted and measured plasma drug concentrations is limited by physiological, mechanical, procedural, and analytical factors and by Model misspecification but has not been an obstacle to clinical utilization of these devices. Model-DRIVEN DRUG DELIVERY Computerized Pharmacokinetic Model-driven administration of iv drugs [l], which is referred to by us as CACI (computerassisted Gontinuous infusion), is being investigated by researchers in several countries, particularly as a tool to deliver iv anesthetic drugs. CACI is undergoing commercial development in the US. With CACI, drug administration is based on theoretical plasma drug concentrations (Cp) rather than dosage.
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Algorithm for optimal linear Model-based control with application to Pharmacokinetic Model-driven drug delivery
IEEE Transactions on Biomedical Engineering, 1990Co-Authors: J.r. JacobsAbstract:Computerized Pharmacokinetic-Model-driven administration of intravenous anesthetic agents has been implemented using a variety of algorithms to control the drug infusion regimen. All such algorithms are similar to the extent that they use a linear Pharmacokinetic Model of the drug being administered to determine drug infusion rates that theoretically achieve and maintain plasma drug concentrations (setpoints) specified by the physician. Since the behavior of the Pharmacokinetic Model can be computed for any input, it should be possible to achieve regulation of the drug infusion rates that is flexible (i.e. the physician can interactively adjust the setpoint), practical, and analytically optimized; these objectives are realized by the algorithm described.
Michael S Strano - One of the best experts on this subject based on the ideXlab platform.
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a Pharmacokinetic Model of a tissue implantable cortisol sensor
Advanced Healthcare Materials, 2016Co-Authors: Naveed A Bakh, Gili Bisker, Emery N Brown, Michael S StranoAbstract:Cortisol is an important glucocorticoid hormone whose biochemistry influences numerous physiological and pathological processes. Moreover, it is a biomarker of interest for a number of conditions, including posttraumatic stress disorder, Cushing's syndrome, Addison's disease, and others. An implantable biosensor capable of real time monitoring of cortisol concentrations in adipose tissue may revolutionize the diagnosis and treatment of these disorders, as well as provide an invaluable research tool. Toward this end, a mathematical Model, informed by the physiological literature, is developed to predict dynamic cortisol concentrations in adipose, muscle, and brain tissues, where a significant number of important processes with cortisol occur. The Pharmacokinetic Model is applied to both a prototypical, healthy male patient and a previously studied Cushing's disease patient. The Model can also be used to inform the design of an implantable sensor by optimizing the sensor dissociation constant, apparent delay time, and magnitude of the sensor output versus system dynamics. Measurements from such a sensor would help to determine systemic cortisol levels, providing much needed insight for proper medical treatment for various cortisol-related conditions.
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a Pharmacokinetic Model of a tissue implantable insulin sensor
Advanced Healthcare Materials, 2015Co-Authors: Gili Bisker, Nicole M Iverson, Michael S StranoAbstract:While implantable sensors such as the continuous glucose monitoring system have been widely studied, both experimentally and mathematically, relatively little attention has been applied to the potential of insulin sensors. Such sensors can provide feedback control for insulin infusion systems and pumps and provide platforms for the monitoring of other biomarkers in vivo. In this work, the fi rst Pharmacokinetic Model of an affi nity sensor is developed for insulin operating subcutaneously in the limit of where mass transfer across biological membranes reaches a steady state. Using a physiological, compartmental Model for glucose, insulin, and glucagon metabolism, the maximum sensor response and its delay time relative to plasma insulin concentration, are calculated based on sensor geometry, placement, and insulin binding parameters for a sensor localized within adipose tissue. A design relation is derived linking sensor dynamics to insulin time lag and placement within human tissue. The Model should fi nd utility in understanding dynamic insulin responses and forms the basis of Model predictive control algorithms that incorporate sensor dynamics.
G N C Kenny - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetic Model driven infusion of propofol in children
BJA: British Journal of Anaesthesia, 1991Co-Authors: B Marsh, M White, N S Morton, G N C KennyAbstract:A computer controlled infusion device for propofol was used to induce and maintain general anaesthesia in 20 children undergoing minor surgical procedures. The device was programmed with an adult Pharmacokinetic Model for propofol. During and after anaesthesia, blood samples were taken for measurement of propofol concentrations and it was found that the values obtained were systematically over-predicted by the delivery system algorithm. New Pharmacokinetic microconstants were derived from our data which reflected more accurately the elimination and distribution of propofol in a prospective study involving another 10 children.
J Den G Hollander - One of the best experts on this subject based on the ideXlab platform.
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alteration of postantibiotic effect during one dosing interval of tobramycin simulated in an in vitro Pharmacokinetic Model
Antimicrobial Agents and Chemotherapy, 1996Co-Authors: J Den G Hollander, M P J Van Goor, Frank P Vleggaar, Johan W. Mouton, Henri A VerbrughAbstract:The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro Pharmacokinetic Model simulating human Pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the Model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable.
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killing of pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro Pharmacokinetic Model
Antimicrobial Agents and Chemotherapy, 1994Co-Authors: Johan W. Mouton, J Den G HollanderAbstract:An in vitro Pharmacokinetic Model mimicking human serum drug concentrations, based on a dialyzer unit, was developed to study the efficacies of continuous infusion and intermittent administration of ceftazidime over a period of 36 h. The daily dose of ceftazidime was 300 mg/liter/24 h given either as a continuous infusion or as three bolus doses. The intermittent dosing regimen yielded peak and trough concentrations after the fourth dose of 92.3 (standard deviation, 8.0) and 1.4 (standard deviation, 0.9) mg/liter, respectively. Continuous administration yielded concentrations of approximately 20 mg/liter. To study efficacy, three Pseudomonas aeruginosa strains, ATCC 27853, CF4, and CF16, were used. The MICs of ceftazidime for these strains were 1, 4, and 16 mg/liter, respectively. Strain CF16 was killed initially during both regimens and then started to regrow. At the end of the fourth dosing interval, i.e., after 32 h, viable counts showed no difference between the regimens. Strains ATCC 27853 and CF4 were killed initially during both dosing schedules, and after the first dosing interval viable counts were similar. However, after the fourth interval, there was a marked difference between bacterial counts during continuous and intermittent infusion, being 2.2 and 2.8 log10, respectively, demonstrating a greater efficacy during continuous infusion. The results indicate that, in the absence of other factors, a sustained level of ceftazidime around or slightly above the MIC is not high enough to maintain efficacy over more than one (8-h) dosing interval. When sustained concentrations higher than four times the MIC are employed, continuous administration in this Model is more efficacious than intermittent dosing.
E.a. Williams - One of the best experts on this subject based on the ideXlab platform.
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Algorithm to control "effect compartment" drug concentrations in Pharmacokinetic Model-driven drug delivery
IEEE Transactions on Biomedical Engineering, 1993Co-Authors: J.r. Jacobs, E.a. WilliamsAbstract:In most computer-controlled Pharmacokinetic Model-driven drug infusion pumps, simulation of a linear compartmental Pharmacokinetic Model is used to compute the rate of intravenous drug infusion required to achieve setpoint central compartment (plasma) drug concentrations. For many drugs, it has been suggested that it is the drug concentration in a hypothetical "effect" compartment, rather than in the plasma, that should be manipulated to achieve maximum control over pharmacologic action. Controlling the effect compartment drug concentration is algorithmically more difficult than controlling the central compartment drug concentration because of the time delay between administration of drug into the central compartment and its subsequent appearance in the effect compartment. The authors present a Model-based dosing algorithm for use in Pharmacokinetic Model-driven drug infusion devices that target the theoretical effect compartment drug concentration.
