Nonlinear dynamics and chaos theory: Concepts and applications relevant to pharmacodynamics

被引:31
作者
Dokoumetzidis, A
Iliadis, A
Macheras, P [1 ]
机构
[1] Univ Athens, Sch Pharm, GR-10679 Athens, Greece
[2] Univ Mediterranee, Dept Pharmacokinet, Marseille, France
关键词
pharmacodynamics; chaos; cardiovascular drugs; CNS drugs; hormones;
D O I
10.1023/A:1011083723190
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:415 / 426
页数:12
相关论文
共 68 条
[11]   A population growth model of dissolution [J].
Dokoumetzidis, A ;
Macheras, P .
PHARMACEUTICAL RESEARCH, 1997, 14 (09) :1122-1126
[12]   An alternative method for the estimation of the terminal slope when a few data points are available [J].
Dokoumetzidis, A ;
Iliadis, A ;
Macheras, P .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 88 (05) :557-560
[13]   MORTALITY AND MORBIDITY IN PATIENTS RECEIVING ENCAINIDE, FLECAINIDE, OR PLACEBO - THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL [J].
ECHT, DS ;
LIEBSON, PR ;
MITCHELL, LB ;
PETERS, RW ;
OBIASMANNO, D ;
BARKER, AH ;
ARENSBERG, D ;
BAKER, A ;
FRIEDMAN, L ;
GREENE, HL ;
HUTHER, ML ;
RICHARDSON, DW .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (12) :781-788
[14]  
Ehlers CL, 1998, J NEUROSCI, V18, P7474
[15]   Nonlinear EEG analysis and its potential role in epileptology [J].
Elger, CE ;
Widman, G ;
Andrzejak, R ;
Arnhold, J ;
David, P ;
Lehnertz, K .
EPILEPSIA, 2000, 41 :S34-S38
[16]   Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial [J].
Exner, DV ;
Reiffel, JA ;
Epstein, AE ;
Ledingham, R ;
Reiter, MJ ;
Yao, Q ;
Duff, HJ ;
Follmann, D ;
Schron, E ;
Greene, HL ;
Carlson, MD ;
Brodsky, MA ;
Akiyama, T ;
Baessler, C ;
Anderson, JL .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1999, 34 (02) :325-333
[17]   Modeling a bivariate control system: LH and testosterone response to the GnRH antagonist antide [J].
Fattinger, KE ;
Verotta, D ;
Porchet, HC ;
Munafo, A ;
leCotonnec, JY ;
Sheiner, LB .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1996, 271 (04) :E775-E787
[18]   MATHEMATICAL-MODEL FOR INVIVO PHARMACODYNAMICS INTEGRATING FLUCTUATION OF THE RESPONSE - APPLICATION TO THE PROLACTIN SUPPRESSANT EFFECT OF THE DOPAMINOMIMETIC DRUG DCN 203-922 [J].
FRANCHETEAU, P ;
STEIMER, JL ;
DUBRAY, C ;
LAVENE, D .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1991, 19 (03) :287-309
[19]  
FREEMAN KA, 1994, J PHARMACOL EXP THER, V268, P629
[20]   Preventing ventricular fibrillation by flattening cardiac restitution [J].
Garfinkel, A ;
Kim, YH ;
Voroshilovsky, O ;
Qu, ZL ;
Kil, JR ;
Lee, MH ;
Karagueuzian, HS ;
Weiss, JN ;
Chen, PS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) :6061-6066