Introduction to PK - Distribution
Hi everyone,
In this session we’ll be dealing with the process that occurs immediately following absorption – that is, Distribution.
Now when a drug is administered, it achieves a certain concentration and then that concentration falls and eventually all the drug is eliminated. We will deal with the elimination process in the next video, but for now, I want you to focus on the events occurring after drug enters the circulation, but before any elimination has taken place.
At this theoretical point in time, the concentration of the drug is denoted as C0, or Concentration at zero time. At this point in time, the concentration is just the administered dose of the drug divided by a theoretical volume of distribution. So there is really no mystery to the concept of the volume of distribution. It is merely a volume term, assuming the entire body can be represented by the plasma, which relates the administered dose to the observed concentration at zero-time.
If the administered drug remains localized to the circulation, as in the case of a highly protein bound drug, the volume of distributions is more or less that of the circulation, and relatively small.
If however, the drug is uniformly distributed throughout the body, as if the body behaves like a container filled with plasma, the volume of distribution is pretty much the physical volume of the body.
In most cases, the drug is not distributed is not distributed homogeneously throughout the body and may be preferentially trapped in certain tissue and organs. In such cases, the observed plasma concentration is very low, and conveys the impression that the volume of distribution is very large, and much larger than the physical volume of the body.
So how will it help us to know about the volume of distribution? Well, for starters, it will help us get an idea of the starting concentrations in the circulation. And if we have a target concentration in mind, knowing the volume of distribution will help us devise a starting dose regiment.
Here are some graphs to show you the impact of changing the volume of distribution. You can see that reducing the volume of distribution proportionately increases concentration at zero-time. Note particularly that because the volume is smaller, the elimination is faster and the half-life is decreased.
In a multiple dose situation, you can see that because the half-life is reduced, the time to reach steady state occurs earlier. Reducing the volume of distribution also increases the fluctuations although the average concentrations are unchanged. We’ll talk about this a bit more in subsequent videos, but just make a note of this for now.
The volume of distribution can vary quite a bit between individuals and populations. It is affected primarily by body weight, body proportions, the permeability characteristics of the drug, the expression of transporters on biological membranes and certain food and drug interactions.
I hope by now, you have an understanding of the distribution process affecting a typical drug, and can appreciate the impact that it may have on therapeutics. In the next video we will discuss what happens after distribution, - how the drug is cleared from the body. See you again soon.