Концепція фізіологічної транзитно-реверсійно-метаболічної моделі всмоктування лікарських засобів

Abstract

In this article we have tried to prove experimentally the views on this issue and on the basis of the data obtained to establish an appropriate concept of absorption of drugs, which we called physiological transit-reverse-metabolic model. In related studies we used the following compounds: ethanol, acetaldehyde and acetic acid. Their choice was dictated by the fact that they do not bind to plasma proteins, allowing the compounds involved in the absorption and reabsorption. Furthermore, these substances are interrelated metabolic processes. Ethyl alcohol is a substrate for alcohol dehydrogenase and acetaldehyde — aldehyde dehydrogenase. Finally, ethanol is absorbed in the digestive tract (stomach and intestine) paracellular mechanism by simple diffusion, and acetic acid — transcellular using carrier. It was also shown that ethanol is transit along the gastrointestinal tract, metabolism and reabsorption (reversion) of blood. This model consists of three interlinked submodels for alcohol (ethanol), aldehydes (acetaldehyde), and acid (acetic acid). Each sub-model has four compartments — suction (GI) tract, metabolism (blood), distribution (tissue) and metabolism (liver). The proposed model can work in private or in open chambers. In the future, for the chain of metabolic transformations of ethanol → acetaldehyde we proposed to extend our basic model by using some assumptions. For ethanol and acetaldehyde, we propose to use a limited perfusion model as their distribution is dependent on the speed of transport to the tissues and not the speed at which they are absorbed. In the simulation of such a system was considered the perfusion rate through each organ (tissue), the physical connection between the authorities and the metabolic activity of ethanol and acetaldehyde. For a physiological model, we are the basic mass balance equation. Presented physiological model to a greater extent corresponds to the process of metabolism and distribution of ethanol and its metabolite. In our opinion, one may adapt this scheme for other compounds as well, but it is necessary to take into account the chain of metabolic transformations and the constants characterizing the metabolism (constant primary metabolism, the affinity constant for the liver and the maximum rate of metabolism in the liver).

Модель состоит из трех взаимосвязанных подмоделей для спирта (этанол), альдегида (ацетальдегид) и кислоты (уксусная кислота). Каждая подмодель имеет четыре отсека — для всасывания (ЖКТ), обмена (кровь), распределения (ткани) и метаболизма (печень). Предложенная модель может работать как в закрытых, так и в открытых камерах. В дальнейшем для цепи метаболических превращений этанол → ацетальдегид мы предложили расширить нашу базовую модель. При моделировании в такой системе были учтены скорость перфузии через каждый орган (ткань), физическая связь между органами и метаболическая активность этанола и ацетальдегида. Для такой физиологической модели нами приведены основные уравнения баланса масс. Представленная физиологическая модель в большей степени соответствует процессам метаболизма и распределения этанола и его метаболита.