An approach to the modeling of the tolerance mechanism in the drug effect. I: The drug effect as a disturbance of regulations.

In this paper the disturbing effect of drugs upon regulation in the organism is argued to be an important factor in the total drug effect. It is made plausible that the decrease of the drug effect after prolonged or repeated administration of the drug is caused by the adaptation of the involved regulations to the presence of the drug, the adaptive process being selective for the drug in question. A model based on these assumptions is developed taking into account the specific behaviour of regulated processes. The functioning of the model is investigated by means of computer simulations. The behaviour of the model appears to be well in accordance with the phenomenon of drug tolerance as described in literature.