Tissue distribution (cont.)
Now assume that the 12 units of drug do not distribute evenly into the plasma and interstitial layer of fluid. In this example, 8 units of the drug are bound to the wall of the interstitial layer. Now only 3 units are free in the interstitial fluid layer. For the concentration to be equal in both the plasma and interstitial tissue, there is now 1 and 3 units respectively with a concentration of 1 unit/3 litre = 0,33 units/litre. Now if we determine the volume of distribution, we find that 12 units (the dose) at 0,33 units/litre (= unit plasma concentration) will give us a volume of 36 litres. But we know that there is no more than 5 litres of blood. This demonstrates that the volume of distribution is an apparent value and does not reflect a real physiological volume. Thus, a volume of distribution that is larger than the blood volume just signifies that the drug is distributed predominantly to other body fluids than blood.
The lower illustration provides some examples of drugs with various apparent volumes of distribution.
Now returning to the gentamicin example. What is the apparent volume of distribution if a 160 mg intravenous injection of gentamicin in a 70 kg man produces a concentration of 7 μg/mL?
Unfortunately, this measured concentration is lower than the desired peak of >8 μg/mL. Therefore, what dose would you give to achieve doses around 10.5 μg/ml?
Gentamicin dose = 240 mg