Recirculatory Pharmacokinetic Modeling

Krejcie, Tom C.; Avram, Michael J.

doi:10.1213/ane.0b013e318240139b

Cited by 12 publications

(5 citation statements)

References 19 publications

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“…Although the combination of AS and MQ constitutes a PK mismatch, there has been no decline in the in vitro susceptibility of parasites to MQ during a 5-year study period; in fact, the sensitivity to MQ has increased significantly. This contrasts with a 40% decrease in efficacy in vivo to MQ in the 5 years before the study [47]. Cure rates with AS-MQ remain almost 100%.…”

Section: Pk Mismatch Does Not Lead To Emergence Of Resistance To Actsmentioning

confidence: 80%

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Basic Pharmacokinetic Concepts and Some Clinical Applications

Ahmed¹

2015

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Over the years, Dr. Tarek gained vast experience and excellent teaching skills through his handling of all of the pharmaceutical practical and theoretical courses for undergraduate and postgraduate students, especially those that deal with pharmacokinetics and biopharmaceutics. Besides his teaching skill, Dr. Tarek has a lot of international publications in different pharmaceutical scientific research journals such as

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Section: Pk Mismatch Does Not Lead To Emergence Of Resistance To Actsmentioning

confidence: 80%

“…The effect of reduced distribution clearance is to reduce the initial plasma concentrations after drug administration. This is particularly important in drugs with rapid onset such as anesthetics [47]. Recirculatory models may help to evaluate the initial distribution and pharmacodynamic response of this type of drugs.…”

Section: Drug Distributionmentioning

confidence: 99%

Basic Pharmacokinetic Concepts and Some Clinical Applications

Ahmed¹

2015

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“…Full PBPK models have representations of the major organs of the body. In contrast, Semi‐PBPK or ‘Recirculatory’ models may use pooling or lumping where different regions or organs of the body are represented as a single kinetic system. This may be useful where a particular organ of the body is of particular interest (e.g., the brain for anesthetics ) but kinetics in the remainder of the body can be represented as one, two, or three lumped compartments.…”

Section: Modeling Strategiesmentioning

confidence: 99%

An introduction to physiologically‐based pharmacokinetic models

Upton

Foster

Abuhelwa

2016

Pediatric Anesthesia

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Physiologically-based pharmacokinetic (PBPK) models represent drug kinetics in one or more 'real' organs (and hence require submodels of organs/tissues) and they describe 'whole-body' kinetics by joining together submodels with drug transport by blood flow as dictated by anatomy. They attempt to reproduce 'measureable' physiological and/or pharmacokinetic processes rather than more abstract rate constants and volumes. PBPK models may be built using a 'bottom-up' approach, where parameters are chosen from first principles, literature, or in vitro data as opposed to a 'top-down' approach, where all parameters are estimated from data. The basic principles of PBPK models are described, focusing on the equations for three individual organs: a single flow-limited compartment describing distribution only, a membrane-limited compartment describing distribution, and a single flow-limited compartment with elimination. These organ models are linked to make a basic three-compartment physiological model of the whole body. PBPK models are particularly suited to scaling kinetics across body size (e.g., adult to neonate) and species (e.g., animal to first-in-man) as physiology and pharmacology can be represented by independent parameters. Maturation models can be incorporated as for compartmental models. PBPK models are now available in commercial software packages, and are perhaps now more accessible than ever. Alternatively, even complex PBPK models can be represented in generic differential equation-solving software using the simple principles described here. The relative ease of constructing the code for PBPK models belies the most difficult aspect of their implementation-collecting, collating, and justifying the data used to parameterize the model.

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“…This is particularly important in drugs with rapid onset such as anesthetics [47]. Recirculatory models may help to evaluate the initial distribution and pharmacodynamic response of this type of drugs.…”

Section: Drug Distributionmentioning

confidence: 99%

“…The inclusion of pulmonary drug uptake, cardiac output, and its regional disposition enables recirculatory models to identify the pharmacokinetic basis of interindividual differences in response to IV anesthetics attributable to age, disease, or druginduced physiological disturbances. They can also be used to design target-controlled drug infusions (which do not result in early drug concentrations in excess of the target be-cause of overestimation of the initial distribution volume) and to estimate pharmacodynamic parameters with greater precision [47].…”

Section: Drug Distributionmentioning

confidence: 99%