Interaction of drug absorption in step (for example, oral drugs) – transport processes of drugs through biomembranes
To the drug from the site of administration into the systemic circulation acted, they must pass through several semipermeable cell membranes (except in the case of intravenous). Biomembrany are bilayer lipid matrix, which includes protein macromolecules of various sizes and composition. They serve as biological barriers, selectively prevents the penetration of molecules in the blood of a particular structure.
Molecules of most drugs pass through the cell membrane by passive diffusion, moving from a region of high concentration (eg, from the gastrointestinal tract) in the region of low concentration (blood) without the cost of energy. The rate of this diffusion is proportional to the concentration gradient of the substance and depends on its solubility in lipids, degree of ionization, molecular size and surface area, through which the diffusion. This concentration gradient is the driving force and absorption. The un-ionised compounds and substances, having a small molecular size, diffuse through the lipid membrane is much easier compared to the Navy and the ionized substances. Transport past may hinder the availability of cell surface charged groups.
The equilibrium transmembrane distribution of the weak electrolyte is determined by the pKa of the compound and the pH gradient. The degree of ionization of weak electrolytes on both sides of the membrane varies. For Example, any acid having a pKa 4,4 plasma (pH 7,4) the concentration ratio of ionized and non-ionized forms of the same 1:1000; in gastric juice (pH 1,4) - The ratio, contrary 1000:1. If ingestion of a weak acid concentration gradient is established, favoring its diffusion through the stomach lining into the blood plasma. For a weak base with a pKa 4,4 the situation is reversed. Thus, drug substance, It is in the form of a weak acid, such acetylsalicylic, It must be absorbed from the gastric juice better, The weaker base, for example quinidine. However, regardless of the pH of the medium, most drugs are better absorbed in the small intestine (pH 5-8). This contradiction is explained by a much greater surface area of the suction and higher permeability of cell membranes in the small intestine.
Some drugs, such as glucose and others., capable of penetrating through the membrane via facilitated diffusion, which suggests the presence of a carrier, capable of reversibly binding to a specific configuration of connections, to carry them through the biomembrane and release inside the cell. For such a mediated diffusion characteristic selectivity, saturation and lack of energy costs (substances are not transported against a concentration gradient).
Substance in the form of ions, vitamins, sugar, amino acids and other compounds, similar in structure to the components of body tissues, can diffuse through the membrane by an active transport - Process, characterized by selective. It requires energy expenditure, the substrate can be moved against a concentration gradient. Such compounds are typically absorbed at specific portions of the small intestine.
Very rarely, drugs are transported through the body pinocytosis, t. it is. by cellular uptake of particles or liquids.
