Distribution is the delivery of drug from the systemic circulation to tissues. Once a drug has entered the blood compartment, the rate at which it penetrates tissues and other body fluids depends on several factors. These include (1) capillary permeability, (2) blood flow-tissue mass ratio (i.e., perfusion rate), (3) extent of plasma protein and specific organ binding, (4) regional differences in pH, (5) transport mechanisms available, and (6) the permeability characteristics of specific tissue membranes.
Drug delivery and eventual drug equilibration with intercellular tissue spaces are largely determined by the extent of organ blood flow. The composition of the capillary bed is usually not a limiting factor except with the capillaries of the CNS. The renal and hepatic capillaries are especially permeable to the movement of most molecules, except those of particularly large size. The rate of passage of drugs across capillary walls can be influenced by agents that affect capillary permeability (e.g., hista-mine) or capillary blood flow rate (e.g., norepineph-rine).
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