1) The drug may remain largely within the vascular system. Plasma substitutes such as dextran are an example of this type, but drugs which are strongly bound to plasma protein may also approach this pattern.
2) Some low molecular weight water soluble compounds such as ethanol and a few sulfonamides become uniformly distributed throughout the body water.
3) A few drugs are concentrated specifically in one or more tissues that may or may not be the site of action. Iodine is concentrated by the thyroid gland. The antimalarial drug chloroquine may be present in the liver at concentrations 1000 times those present in plasma. Tetracycline is almost irreversibly bound to bone and developing teeth. Consequently tetracyclines should only be given to young children or infants in extreme conditions as it can cause discoloration and mottling of the developing second set of teeth. Another type of specific concentration may occur with highly lipid soluble compounds which distribute into fat tissue.
4) Most drugs exhibit a non-uniform distribution in the body with variations that are largely determined by the ability to pass through membranes and their lipid/water solubility. The highest concentrations are often present in the kidney, liver, and intestine usually reflecting the amount of drug being excreted.
Pattern 4 is the most common being a combination of patterns 1, 2 and 3.
Diagram XVIII-1 Representing Various Volumes Distribution Patterns
Table XVIII-1 Apparent Volumes of Distribution
94 - 250
6600 - 17500
A useful indicator of the type of pattern that characterizes a particular drug is the apparent volume of distribution.
A value of V in the region of 3-5 liter (in an adult) would be compatible with pattern 1. This is approximately the volume of plasma. Pattern two would be expected to produce a V value of 30 to 50 liter, corresponding to total body water. Agents or drugs exhibiting pattern 3 would exhibit very large values of V if the drug concentration effect was acting on most of the dose. Chloroquine has a V value of approximately 17,000 liter. Drugs following pattern 4 may have a V value within a wide range of values. These patterns of variation have been used to determine body fluid volumes.
Table XVIII-2 Volumes Measured by Various Test Materials
|Fluid substances||Volume (liter)||Test|
|Extracellular Fluid||13-16||Inulin, Na23, Br-, I-|
|Plasma||3-4||Evans blue, I131 albumin, dextrans|
|Total body water||40-46||Antipyrine, D2O, ethanol|
Copyright 2001 David W.A. Bourne