A Modern View of Pharmacokinetics

Wagner, John G.

doi:10.1007/978-1-4684-2055-5_3

Cited by 8 publications

(8 citation statements)

References 128 publications

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“…A major feature of our modeling procedure was that we looked for a single model, with just one set of parameter values defining a given compartmental structure, that could describe the entire set of data, including dose dependence. As asserted by Wagner (41), nonlinearities can be recognized in such a situation, but the corollary is that these nonlinearities significantly influence the identified kinetic behavior and the a priori identifiability. The nonlinearities of intrinsic or extrinsic origin become part of the model structure and are thus important for the model kinetic response.…”

Section: Discussionmentioning

confidence: 99%

A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building

Staub

Foos

Courtin

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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A model of Sr metabolism was developed by using plasma and urinary Sr kinetic data obtained in groups of postmenopausal women who received four different oral doses of Sr and collected during the Sr administration period (25 days) and for 28 days after cessation of treatment. A nonlinear compartmental formalism that is appropriate for study of non-steady-state kinetics and allows dissociation of variables pertaining to Sr metabolism (system 1) from those indirectly operating on it (system 2) was used. At each stage of model development, the dose-dependent model response was fitted to the four sets of data considered simultaneously (1 set per dose). A seven-compartment model with internal Sr distribution and intestinal, urinary, and bone metabolic pathways was selected. It includes two kinds of nonlinearities: those accounting for saturable intestinal and bone processes, which behave as intrinsic nonlinearities because they are directly dependent on Sr, and extrinsic nonlinearities (dependent on system 2), which suggest the cooperative involvement of plasma Sr changes in modulating some intestinal and bone mineral metabolic pathways. With the set of identified parameter values, the initial steady-state model predictions are relevant to known physiology, and some peculiarities of model behavior for long-term Sr administration were simulated.

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Section: Discussionmentioning

confidence: 99%

A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building

Staub

Foos

Courtin

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…After 12 hours the linear relationship between drug levels and time had disappeared. As only one dose level was used in these experiments the results must be interpreted very cautiously (WAGNER 1974). One factor that may contribute to this non-linearity of the curves is accumulation of metabolites which interfere with the plasma determinations of the unchanged drug at low concentrations (MJORNDAL & ORELAND 1971).…”

Section: Resultsmentioning

confidence: 99%

Biochemical and Behavioural Effects of Thiothixene: Relation to Tissue Levels of the Drug

Mjörndal

Wiesel

Oreland

1976

Acta Pharmacologica et Toxicologica

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Male Sprague‐Dawley rats were given a single intraperitoneal dose of a thioxanthene neuroleptic, thiothixene. The effect on the spontaneous motor activity and the level of homovanillic acid in the striatum and the olfactory tubercle were studied at various times after the injection of the drug. The concentration of thiothixene in the blood and brain was also followed. The rats showed a significant decrease in motor activity from 15 min. to 12 hours after the injection. The HVA‐levels in the striatum and olfactory tubercle were significantly elevated from 0.5 to 18 hours, the effect on the striatum being relatively more pronounced. No clear relation between drug levels and changes in motor activity of HVA‐levels was found.

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“…On the fifth step of the model development process, a) the output C(s) of the model developed corresponding to the ethanol input I(s) was determined, using a numerical simulation method in the time domain; After that the model output C(s) was refined, using the Gauss-Newton and Monte-Carlo method [31,32] in the time domain. After that, the outcomes of the models developed and the concentration-time profiles of ethanol were mutually statistically compared, and in this way, a validation on the models was performed [33][34][35][36][37][38] .…”

Section: Methodsmentioning

confidence: 99%

Evaluation of arterial-venous blood alcohol concentration gradients of ethanol administered by an infusion to dogs

Ďurišová¹,

Internationals²

2018

JPP

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Numerous workers investigated ethanol pharmacokinetic. Therefore, the goal of the present study was not an investigation of ethanol pharmacokinetics; instead, the goal of the present study was to prepare further illustrative examples of a successful use of computational and modeling tools from system engineering in pharmacokinetic investigations. The previous study by Wilkinson and Rheingold published in October 1977 issue of the Journal of Pharmacokinetics, described an investigation of arterial-venous blood concentration gradients of ethanol administration by a constant rate intravenous infusion through indwelling venous catheters to dogs. The present study is a free continuation of the study by Wilkinson and Rheingold; therefore, the data available in the study by Wilkinson and Rheingold were used. An advanced modeling method, implemented in the computer program named CTDB, and described in the study by Dedik et al [1] was used for modeling purposes.

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A Modern View of Pharmacokinetics

Cited by 8 publications

References 128 publications

A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building

A nonlinear compartmental model of Sr metabolism. I. Non-steady-state kinetics and model building

Biochemical and Behavioural Effects of Thiothixene: Relation to Tissue Levels of the Drug

Evaluation of arterial-venous blood alcohol concentration gradients of ethanol administered by an infusion to dogs

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