CXT-MAIN: a software package for determination of the analytical form of the pharmacokinetic system weighting function

Dedik, Ladislav; Ďurišová, M

doi:10.1016/s0169-2607(96)01770-1

Cited by 20 publications

(43 citation statements)

References 12 publications

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“…In general, if dynamic systems are modeled using a transfer function model; as it was the case in the current study (see Eq. (2)), then the accuracy of the models developed depends on the degrees of the polynomials of the transfer function model used to fit the data, see for example the following studies [7][8][9][10][11][12][13][14][15][16], and references therein.…”

Section: Discussionmentioning

confidence: 99%

“…In the first step, a pharmacokinetic dynamic system, denoted by H was defined in the complex domain, using the Laplace transform of the mathematically described mean serum concentration-time profile of acetaminophen of adult male Sprague-Dawley rats, denoted by (S) C and the Laplace transform of the mathematically described intramuscular administration of acetaminophen to adult male Sprague-Dawley rats, denoted by I(S) [6][7][8][9][10][11][12][13][14][15][16][17].…”

Section: Methodsmentioning

confidence: 99%

“…Throughout the current study the lower case letter " S " denotes the complex Laplace variable [7][8][9][10][11][12][13][14][15][16]. See the following equation:…”

Section: Methodsmentioning

confidence: 99%

“…They were used to mathematically describe static and dynamic properties of the pharmacokinetic behavior of acetaminophen [18][19][20] in the male Sprague-Daley rats investigated in the previous study by Bélander et al [1]. The modeling method used in the current study has been described in detail in the studies published previously [7][8][9][10][11][12][13][14][15][16], authored or co authored by the author of the current study. Therefore a description of the modeling method used was not given here.…”

Section: Venous Serum Concentration Of Acetaminophen (µG/ml)mentioning

confidence: 99%

“…The current study is a companion piece of the study by Belander et al [1]. Therefore the data available in the study [1] was used with the objective to provide a further example showing a successful use of an advanced mathematical modeling method based on the theory of dynamic systems in mathematical modeling in pharmacokinetics [6][7][8][9][10][11][12][13][14][15][16]. Previous examples showing an advantageous use of the modeling method used in the current study can be found in the full-text journal articles available online, which can be downloaded completely, free of charge, from the following web sites of the author: http:// www.uef.sav.sk/durisova.htm and http://www.uef.sav.sk/ advanced.htm…”

Section: Introductionmentioning

confidence: 99%

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Untitled

2016

JAPLR

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Throughout the current study the lower case letter " S " denotes the complex Laplace variable [7][8][9][10][11][12][13][14][15][16]. See the following equation:…”

Section: Methodsmentioning

confidence: 99%

Section: Venous Serum Concentration Of Acetaminophen (µG/ml)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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2016

JAPLR

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Classical Michaelis-Menten and system theory approach to modeling metabolite formation kinetics

Popović

2004

European Journal of Drug Metabolism and Pharmacokinetics

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When single doses of drug are administered and kinetics are linear, techniques, which are based on the compartment approach and the linear system theory approach, in modeling the formation of the metabolite from the parent drug are proposed. Unlike the purpose-specific compartment approach, the methodical, conceptual and computational uniformity in modeling various linear biomedical systems is the dominant characteristic of the linear system approach technology. Saturation of the metabolic reaction results in nonlinear kinetics according to the Michaelis-Menten equation. The two compartment open model with Michaelis-Menten elimination kinetics is theorethicaly basic when single doses of drug are administered. To simulate data or to fit real data using this model, one must resort to numerical integration. A biomathematical model for multiple dosage regimen calculations of nonlinear metabolic systems in steady-state and a working example with phenytoin are presented. High correlation between phenytoin steady-state serum levels calculated from individual Km and Vmax values in the 15 adult epileptic outpatients and the observed levels at the third adjustment of phenytoin daily dose (r=0.961, p<0.01) were found.

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Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. I: conceptual and numerical issues

Popović

2006

European Journal of Drug Metabolism and Pharmacokinetics

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A cubic spline function for describing the verapamil concentration profile, resulting from the verapamil absorption input to be evaluated, has been used. With this method, the knots are taken to be the data points, which has the advantage of being computationally less complex. Because of its inherently low algorhythmic errors, the spline method is less distorted and more suitable for further data analysis than others. The method has been evaluated using simulated verapamil delayed release tablet concentration data containing various degrees of random noise. The accuracy of the method was determined by how well the estimates of input rate and extent represented the true values. It was found that the accuracy of the method was of the same order of magnitude as the noise level of the data. Spline functions in convolutional modeling of verapamil formulation bioavailability and bioequivalence, as shown in the numerical simulation investigation, are very powerful additional tools for assessing the quality of new verapamil formulations in order to ensure that they are of the same quality as already registered formulations of the drug. The development of such models provides the possibility to avoid additional or larger bioequivalence and/or clinical trials and to thus help shorten the investigation time and registration period.

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CXT-MAIN: a software package for determination of the analytical form of the pharmacokinetic system weighting function

Cited by 20 publications

References 12 publications

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Untitled

Classical Michaelis-Menten and system theory approach to modeling metabolite formation kinetics

Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. I: conceptual and numerical issues

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