Factors affecting drug distribution

Written by david stewart
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A drug absorbed into the blood must subsequently reach the target tissue. The process of the drug moving from one part of the body to another is known as "drug distribution." This activity depends on several physiological factors as well as the chemical nature of the drug. A thorough knowledge of a drug's distribution pattern is important to determine effective dosing regimens.

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Perfusion Rate

Following their absorption, drugs are transported through the blood to different body parts. Different organs receive varying quantities of blood, expressed in terms of blood perfusion rate. An organ with a higher perfusion rate receives a greater amount of the drug as compared with one with a lower perfusion rate. As a result, drug concentrations rise faster in organs such as the brain, heart, liver and kidneys as compared with skin, bone and muscle.

Permeability of Membranes

Passage of the drugs from the blood into the tissues occurs through the endothelial and epithelial cells lining the capillary walls. Generally, movement of lipid-soluble drugs is easier and faster as compared with water-soluble drugs. Drugs with low molecular weight also diffuse faster into tissues in comparison with those with higher molecular weights. Capillaries in the kidney and liver sinusoids show a greater permeability because of differences in membrane structure. Brain capillaries allow the selective transport of lipid-soluble drugs while severely restricting the transfer of polar ones.

Protein Binding

Plasma contains proteins such as albumins and globulins that bind drugs to differing extents. Albumins show a greater tendency to bind a wide range of drugs --- especially those of an acidic nature. Basic drugs bind to lipoproteins and glycoproteins. Vitamins, steroids and metal ions bind to globulins. The greater the amount of drug bound to plasma proteins, the lesser its distribution out of blood into the tissue. For drugs that are extensively protein-bound, a small change in the binding profile often leads to a major difference in the clinical response.

Tissue Localization

Besides plasma proteins, drugs also bind to several molecules located within the cells. In some cases, these molecules may be the drug receptors and such binding is the basis of the drug's action. In other cases, tissue localisation is simply a phenomenon that occurs because of the chemical nature of the drug and leads to an undesirable effect. A typical example of this effect is the binding of tetracyclines to bones, which leads to discolouration of teeth in children.

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