Link to 1.1.1.2 Distribution Teaching Resources
Link to Problems for Discussion
After the drug reaches the systemic circulation it is then distributed around the body (to different organs, inside cells, etc). This distribution depends on the blood flow to organs and factors about the drug such as: how easily it leaves the blood and enters the interstitial fluid, how easily it crosses the cell membranes and enters cells, whether it is concentrated inside cells, whether it is bound to proteins in the blood and so on. This varies enormously between drugs - for example some large molecules (e.g. mannitol) may not go into cells or even escape from the circulation to any great extent. Whereas drugs such as chloroquine that are highly effective against intracellular infections (malaria) may have concentrations 200 times greater inside cells than in the blood.
Vd is the notional volume, which a dose (D) of drug would be distributed in to achieve the measured blood or plasma concentration before elimination has occurred (c0 represents the calculated concentration at zero time after injection. It is generally calculated by backwards extrapolation of the concentration curve once distribution has occurred; in essence it is the equivalent of assuming complete distribution occurred at time zero).
Those of you who followed that can jump to the next definition.
But as Vd is a difficult concept for many people to understand I will elaborate.
Vd is not a real volume - it is a constant, a tool to estimate or calculate the likely concentration of a drug that will be achieved with a certain dose of drug (using a variation on the above equation C = D/Vd).
Thus in an individual it states that if you double the amount of drug in the body you expect to double the concentration. “Pretty obvious and not terribly useful” I hear you say. Where it becomes useful is that, although the distribution and therefore the Vd for different drugs is extremely varied, people are very similar.
So, it has been observed that the Vd for a given drug is very similar between people-particularly those with similar age, gender, weight, health, etc.
Thus in an individual who has not been exposed to this drug we can predict with considerable accuracy the initial concentration they will achieve for a given dose from a few simple parameters (i.e. weight, age, gender).
[This assumes the drug is given intravenously (IV) or has nearly 100% bioavailability - otherwise it is necessary to also estimate the bioavailability of the dose to calculate the expected blood concentration.]
Secondly the effects of differences in health, etc. are consistent across many drugs. This prediction is not as precise but is very helpful to guide therapy in some individuals.
Thus in an individual who has septic shock we can predict that the volume of distribution for highly water soluble drugs (which generally have small Vd) will be substantially increased (and therefore the concentrations will be lower for any given dose). Conversely, highly lipid soluble drugs (which generally have large Vd) may have reduced volumes of distribution in shocked patients as the blood flow to non-essential parts of the body (such as fat) is reduced.
See also: