How binding of drugs to tissue components affects distribution?
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Drug Distribution to Tissues.
After a drug enters the systemic circulation, it is distributed to the body’s tissues. Distribution is generally uneven because of differences in blood perfusion, tissue binding (eg, because of lipid content), regional pH, and permeability of cell membranes.
The entry rate of a drug into a tissue depends on the rate of blood flow to the tissue, tissue mass, and partition characteristics between blood and tissue. Distribution equilibrium (when entry and exit rates are the same) between blood and tissue is reached more rapidly in richly vascularized areas, unless diffusion across cell membranes is the rate-limiting step. After equilibrium, drug concentrations in tissues and in extracellular fluids are reflected by the plasma concentration. Metabolism and excretion occur simultaneously with distribution, making the process dynamic and complex.
After a drug has entered tissues, drug distribution to the interstitial fluid is determined primarily by perfusion. For poorly perfused tissues (eg, muscle, fat), distribution is very slow, especially if the tissue has a high affinity for the drug.