General Principles Of Pharmacology:Drug Distribution
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Blood Flow
The rate at which a drug reaches different organs and tissues will depend on the blood flow to those regions. Equilibration is rapidly achieved with heart, lungs, liver, kidneys and brain where blood flow is high. Skin, bone, and depot fat equilibrate much more slowly.
Lipid Solubility
Lipid solubility will affect the ability of the drug to bind to plasma proteins and to cross lipid membrane barriers. Very high lipid solubility can result in a drug initially partitioning preferentially into highly vascular lipid-rich areas. Subsequently these drugs slowly redistribute into body fat where they may remain for long periods of time.
Effects of pH
Effects of pH on the partitioning or "trapping" of drugs will not be as dramatic as those seen between the stomach and plasma since the pH differences are not as great. Nevertheless, even small pH differences have significant effects and so acidic drugs will still tend to accumulate where the pH is higher while bases do the reverse.
The rate of movement of a drug out of circulation will depend on its degree of ionization and therefore its pK. Changes in pH occuring in disease may also affect drug distribution. For example, blood becomes more acidic if respiration is inadequate. Also, the pH of milk can increase as much as 0.7 of a pH unit in animals with mastitis.
Capillary Permeability
The ability of a drug to reach various tissues will depend on the permeability of the capillaries at the site in question. For example, the capillaries in liver are extremely permeable, while those at the blood-brain barrier lie at the other extreme. Drugs can pass through the epithelial cells or between them through the gap junctions. Thus, molecular size is the major factor affecting the permeability of water-soluble drugs across capillaries.
Table 3. Characteristics of Barrier Membranes
| Barrier Membrane | Pore Diameter |
| Intestinal epithelium | 4 |
| Capillary endothelium | 40-80 |
| Muscle capillaries | 60 |
| Glomerular capillaries | 75-100 |
| Glomerular endothelium | 1000 |
| Liver capillaries | 1000 |
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