Hi, this tutorial is the second in the pharmacokinetics series, and in this video we're going to have a look at absorption, or more specifically, roots of drug administration. If you haven't seen the previous tutorial, I highly recommend watching it before continuing with this video, as we will use terminology which was introduced and defined in that tutorial. So I'm going to begin by drawing a very simplified body plan.
And this body plan follows the flow of blood from the digestive system to the arterial circulation. So let's see how this happens. So blood flows from the gut to the liver via the hepatic portal system.
Blood then flows from the liver back through the venous circulation and into the right side of the heart. The blood then flows... through the pulmonary arteries to the lungs, then from the lungs back to the left side of the heart, then out into the aorta and into the arterial circulation.
What we are going to do is place drugs into different parts of this system and measure their concentration in the arterial circulation over a period of time. So I'll draw a set of axes, and on the y-axis we have blood concentration of drug, and on the x-axis we have time. We'll begin with the most common route of drug administration, which is orally. These drugs move through the digestive system and get absorbed by the gut, then they move through this whole system, that is, the liver, the venous circulation, the heart, the lungs, back to the heart, and then to the arterial circulation.
This takes quite some time, so what we see is a slow rise in the blood concentration and then a slow fall. Note that the Cmax is quite low and the Tmax is quite large. We'll now contrast that with intravenous administration. Assume that we give the same dose of the drug intravenously, and for those who have read ahead, this drug does not undergo first pass metabolism.
In intravenous or IV administration, the drug doesn't have quite such a long journey to reach the arterial circulation, as it only has to go to the heart, the lungs, back to the heart and then to the arteries. This results in a quicker rise of drug concentration, which might look something like this on the graph. Note that the Cmax is larger and the Tmax is smaller, even though the dose was the same. This is because IV is a more direct route of administration than orally.
Now contrast this with inhalation of a drug. Let's again assume that we have given the same dose of the drug as the last two examples, but this time we are giving it as an inhaled form. Many anaesthetics are actually given this way. The drug now only has to go to the heart and then straight on to the arterial circulation.
This means we will see the concentration of the drug shoot up very quickly. So note the much larger Cmax and the even smaller Tmax via this route of administration. Also remember that in all these three examples the dose of the drug was identical. only the route of administration changed. So you can see how different routes may cause a radically different Cmax and Tmax.
This is important when considering the applications for certain drugs. For instance, if you need pain relief quickly, then an IV analgesic will get into the system much quicker than an oral one. Conversely, a drug which has side effects at high concentrations may be toxic if given intravenously, but the same dose might be safe if given orally.
Now I have three more points I want to make. Firstly, note that the area under the curve is the same for all these routes of administration. This is because the amount of exposure to the drug, that is the dose, is the same.
Just some routes of administration spread the dose out over a greater length of time. Secondly, you might be wondering why the same drug is excreted at different rates, or more simply why curve number 3 falls quicker than curve number 1. Without going into too much detail, I have chosen to show a drug that conforms to first order kinetics. If you don't know what that means, it's okay. We'll cover all this in a later tutorial. But it basically means that the rate of excretion is proportional to the current concentration of the drug.
If the concentration of the drug is high, then it will be excreted faster than if the concentration is low. Also, it's important to note that the half-life of the drug is the same regardless of the route of administration. This is because the half-life is a property of the drug, not the route.
It will take the same amount of time for the drug to reach half of the Cmax of the drug. orally as it will to reach half of the Cmax intravenously. This is because the Cmax is different for each route of administration and the rate of excretion is proportional to the current concentration of the drug.
In the next tutorial we'll look at the metabolism of drugs. In particular we'll look at the actions of cytochrome P450 in the liver. If you've enjoyed this tutorial Please help us produce more by making a donation at www.handwritten-tutorials.com