J E de Bie | PubMed Health

PubMed1991

Chaos and illusion.

Pharmacology is the study of the interaction of drugs with living organisms, especially humans. The body is a very complicated system, which suggests that the 'effect' induced by a drug is not a single entity but a change in several variables at the same time, all of which are interrelated in a nonlinear fashion. Research on nonlinear systems in other fields of science--commonly known as chaos theory--may therefore be of use in understanding pharmacology, as explained here by J. M. van Rossum and J. E. G. M. de Bie. They argue that in the study of drug effects, several variables should be measured simultaneously. Many pharmacologists prefer to construct an illusion of reality, studying just one of the essential variables and averaging data in a population of subjects, thus losing the opportunity to understand what a drug really does to a patient.

Animals↗

PubMed1989

Pharmacokinetics from a dynamical systems point of view.

The pharmacological action of many drugs depends on several variables at the same time and therefore will be dominated by an attractor of a dimension greater than zero. The pharmacokinetic behavior is likely to be dominated by a zero dimensional point attractor so that it is highly predictable. Pharmacokinetics is discussed from a dynamical systems point of view, whereby the transport of drugs in the tissues and organs is considered a stochastic process characterized by density functions of transit times and blood flows. In the body, the tissues and organs are arranged in parallel, in series, and in a feedback-loop fashion. Consequently, the single-pass transport of drugs through the body is again a stochastic process characterized by the density function of total body transit times, the cardiac output, and the total body extraction. The drug molecules, however, may pass through the body several times before ultimately leaving the system by metabolism or excretion. As a result, the body may be regarded as a positive feedback system with the pulmonary circulation (and its tissues) as the forward transfer function and the systemic circulation (with all its tissues) as the feedback transfer function. Consequently, the total body transport function (closed loop) is again a stochastic process characterized by a density function of total body residence times. The relationship between the body transit time distribution and the body residence distribution is determined by the feedback-loop arrangement, the cardiac output, and the extraction ratio which can easily be written in the Laplace domain. The pharmacokinetic parameters logically follow from the systems approach. They are the cardiac output, the mean transit time, the extraction ratio, the clearance, the volume of distribution in steady state, the mean residence time, and the average number of recirculations. The dynamic systems approach in pharmacokinetics has been illustrated with some examples notably with caffeine.

Absorption↗

PubMed1989

Systems dynamics in clinical pharmacokinetics. An introduction.

Pharmacokinetics is in essence the study of the input/output relationships of the (human) body, which is considered as a system characterised by a density function of residence times. The input is the dosage rate, and the output is the concentration in the blood. The body transport function is first derived in a model-independent fashion, assuming linear kinetics. It is subsequently defined on the basis of a positive feedback loop of transport through the pulmonary and systemic circulation. Thus, the residence times distribution is based on transit times distributions and recirculation. The relevant dynamic systems parameters are cardiac output, extraction ratio, clearance, volume of distribution, mean transit time and mean residence time. In the case of drug absorption, mean absorption time and bioavailability are also important. In this review, the systems approach in pharmacokinetics is illustrated by clinical and computational experiments.

Biological Transport↗