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Biomedical subjects

A Dokoumetzidis

Publications and source records attributed to A Dokoumetzidis.

7 recordsLinked to original sources
PubMed2001

Nonlinear dynamics and chaos theory: concepts and applications relevant to pharmacodynamics.

The theory of nonlinear dynamical systems (chaos theory), which deals with deterministic systems that exhibit a complicated, apparently random-looking behavior, has formed an interdisciplinary area of research and has affected almost every field of science in the last 20 years. Life sciences are one of the most applicable areas for the ideas of chaos because of the complexity of biological systems. It is widely appreciated that chaotic behavior dominates physiological systems. This is suggested by experimental studies and has also been encouraged by very successful modeling. Pharmacodynamics are very tightly associated with complex physiological processes, and the implications of this relation demand that the new approach of nonlinear dynamics should be adopted in greater extent in pharmacodynamic studies. This is necessary not only for the sake of more detailed study, but mainly because nonlinear dynamics suggest a whole new rationale, fundamentally different from the classic approach. In this work the basic principles of dynamical systems are presented and applications of nonlinear dynamics in topics relevant to drug research and especially to pharmacodynamics are reviewed. Special attention is focused on three major fields of physiological systems with great importance in pharmacotherapy, namely cardiovascular, central nervous, and endocrine systems, where tools and concepts from nonlinear dynamics have been applied.

Biopharmaceutics↗
PubMed1999

Modeling of supersaturated dissolution data.

A recursion equation which relies on the population growth model of dissolution is used for the analysis of supersaturated dissolution data. The concentration-time data of dissolution experiments are initially transformed to fractions of dose dissolved-generations by adopting an appropriate time interval as the time step of the recursion equation. A computer program is used to derive estimates for the maximum fraction of dose dissolved and the fraction of dose remaining in solution at steady state. Good fittings were observed when this equation was applied to phenytoin and nifedipine supersaturated dissolution data obtained from literature.

Chemistry, Pharmaceutical↗
PubMed1999

An alternative method for the estimation of the terminal slope when a few data points are available.

Phase plane plots are graphical expressions for differential equations plotting the state derivative dc/dt versus the state c. Using these plots, we developed a novel method for the estimation of the terminal slope from time-concentration data. The values of the derivatives used for the construction of the phase plane plots were calculated by two different methods of numerical differentiation. The first method (D1) is based on the classical calculation of slope of the line connecting two successive data points. The alternative method (D2) relies on an initial second-order polynomial interpolation utilizing three successive data points followed by the calculation of the derivative at each one of the concentration values. A forced-through-zero linear regression of the phase plane plot data is used to derive an estimate for the slope. For comparative purposes, the standard approach based on the semilogarithmic plot was also applied. For a hypothetical drug absorbed by first-order process into a one-compartment model, simulated time-concentration data disturbed by a Gaussian zero mean random error with various coefficients of variation were generated. Various sampling schedules, with two, three, four, or five data points, were utilized for the estimation of the terminal slope. Performances of the proposed methods on simulated data were expressed by means of root-mean-squared error, bias, and standard deviation. In all cases, D2 was superior to D1. The D2 method outperforms the standard method in that it furnishes estimates closer to the real values in all cases when two data points and in most cases when three data points were used. All methods behave similarly when four or five data points were used.

Pharmacokinetics↗
PubMed1998

Investigation of absorption kinetics by the phase plane method.

PURPOSE: To develop a simple approach for investigating absorption kinetics, which does not require modeling assumption or intravenous data. METHODS: The concentration (C) -time (t) data are plotted as a phase plane plot (dCldt versus C). Errorless C,t data were generated from one and two compartment models employing first-order, zero-order and Michaelis-menten input kinetics, and the phase plane plots were constructed. A simple test based on the ratio of slopes of the separate linear regression analyses of absorption and elimination data of the phase plane plot is proposed to justify or not the presence of zero order input kinetics. Errant data were used to assess the performance of the test developed. Literature data of theophylline and nitroglycerin formulations were analyzed using the phase plane plot. Input rate-time profiles were constructed for one compartment model drugs utilizing the data of the phase plane plot. RESULTS: The geometric forms of the phase plane plots derived form the errorless data of the various pharmacokinetic models were found to be indicative of the absorption kinetics. Very good resulted were obtained when the test for he discernment of absorption kinetics was applied to errant data. Zero-order absorption kinetics were justified (i) for the transdermal absorption of nitroglycerin and (ii) only for a certain period of time, for the gastrointestinal absorption of theophylline. CONCLUSIONS: Investigation of absorption kinetics can be accomplished with the phase plane method. The cumulative character of the classical percent absorbed versus time plots can be misleading in justifying the presence of zero-order input kinetics.

Absorption↗
PubMed1997

A population growth model of dissolution.

PURPOSE: To develop a new approach for describing drug dissolution which does not require the presuppositions of time continuity and Fick's law of diffusion and which can be applied to both homogeneous and heterogeneous media. METHODS: The mass dissolved is considered to be a function of a discrete time index specifying successive "generations" (n). The recurrence equation: phi n + 1 = phi n + r(1 - phi n)(1 - phi n X0/theta) was derived for the fractions of dose dissolved phi n and phi n+1, between generations n and n + 1, where r is a dimensionless proportionality constant, X0 is the dose and theta is the amount of drug corresponding to the drug's solubility in the dissolution medium. RESULTS: The equation has two steady state solutions, phi ss = 1 when (X0/theta) < or = 1 and phi ss = theta/X0 when (X0/theta) > 1 and the usual behavior encountered in dissolution studies, i.e, a monotonic exponential increase of phi n reaching asymptotically the steady state when either r < theta/X0 < 1 or r < 1 < theta/X0. Good fits were obtained when the model equation was applied to danazol data after appropriate transformation of the time scale to "generations". The dissolution process is controlled by the two dimensionless parameters theta/X0 and r, which were found to be analogous to the fundamental parameters dose and dissolution number, respectively. The model was also used for the prediction of fraction of dose absorbed for highly permeable drugs. CONCLUSIONS: The model does not rely on diffusion principles and therefore it can be applied under both homogeneous and non-homogeneous conditions. This feature will facilitate the correlation of in vitro dissolution data obtained under homogeneous conditions and in vivo observations adhering to the heterogeneous milieu of the GI tract.

Drug Delivery Systems↗