Alright people welcome back!

Let's jump into section two on our series on pharmacokinetics

and we're going to talk about absorption and bioavailability today.

So a quick review from the last lecture. What did we do then?

Well first, we defined pharmacokinetics and you need to know this before we move on.

And so, pharmacokinetics is really looking at the change in drug concentration as the drug moves through the different compartments of the body.

So as the drug moves through your body, how does this concentration change.

And we are going to talk about absorption today and absorption is really the process of a substance entering the systemic circulation.

And so we are going to look at how the concentration changes as a drug enters the systemic circulation

And just a little key point to remember is that absorption is highly dependent on the route of administration.

So let's get to our most important concept of the day first and then we'll get to the good stuff.

So the most important concept. Well this is something that you probably learned in high school.

And what is that?

Concentration is equal to mass over volume.

Super simple. You must know this.

But in terms of pharmacology, what are we talking about?

Well, when we talk about the mass, we're really talking about how much drug we gave right?

If you look at the dosages for most drugs, it's given in milligrams.

So that's referring to mass - the amount of drugs given in milligrams.

Volume is a little variable.

So, if we're talking about blood volume, we want to use you know liters.

If we're talking about the volume in a syringe, we might use cc's or cubic centimeters or milliliters.

I want 5 cc of Epinephrine STAT!

In any case, the volume depends on what you're dissolving it in.

So if a drug is dissolved in a certain volume, and that gives us our concentration.

So what are some common volumes?

Well, blood volume - blood volume is about give or take 5 liters

And commonly used as opposed to blood volume which is not really used when we talk about pharmacokinetics is plasma volume

And so plasma as you know relates to blood and that it's you know

you take the plasma, throw in the - you take the blood, throw in the center fuse, you get out that pale yellow substance and that is your plasma.

And so it's your blood volume - let's just say your blood volume minus the cells.

And your cells make up about 50% of your blood.

So that leaves us with about 50% left and that's about 2.5 liters.

Now on an exam, you might see this actually written in a different way.

So they might write out that your plasma volume is equal your blood volume x 1 minus your Hematocrit.

So remember, hematocrit is what? It's the volume - it's a percentage.

And it's the percentage of your blood volume that the red blood cells take up.

And so, if I was going to multiply this out, I would get blood volume x 1 minus my blood volume x my hematocrit.

Right and that makes sense.

This right here is the cells.

So just in case you saw this a different way.

And finally, just to remind you, 1 cc is 1 cubic centimeter and that is equal to 1 milliliter.

So let's do a problem and solidify this concept.

Concentration is equal to mass over volume.

So a 10 mg dose of drug X is 100% absorbed, what is the plasma drug concentration?

So first off 10mg, that is what?

That is our mass. That is the amount of drug and we know it's 100% absorbed.

So this - the only way anything is ever 100% absorbed is if you give it IV

and when I say absorbed 100% that means it's all getting into the plasma.

It's all getting into the plasma.

So what we want to do is figure out the plasma drug concentration.

So the concentration in the plasma is equal to the mass over the volume.

So what is the mass?

Well the mass is the 10 mg of drug that I gave.

And what is the volume?

Well we just said the volume of the plasma is 2.5 liters.

So overall, I get a concentration of plasma of 4mg/L and we're going to come back to this number on the next slide.

So, here's our case and this is our "in" case

so, we're talking about drugs getting into our body.

So we're going to give a drug IV bolus which means intravenously and bolus means that it's all at once

and it goes into one compartment and that compartment is the plasma.

So this means no distribution.

and we also assume here that there is no elimination.

Honestly, this is the easiest case that we can do.

So we start off by administering this drug IV bolus and we want to get it into our systemic circulation.

So let's just draw a little picture here.

Here is our syringe, we give this drug IV bolus and there's a certain volume of drug in here

and there's a certain concentration of that drug in here.

And so remember, concentration is equal to what?

Concentration is equal to mass divided by volume.

We'll get back to this in one second.

So what we want to do is draw a little graph

and on the Y axis of this graph, we're going to put the plasma drug concentration.

and on the X axis, we're going to put time.

And so if I'm going to draw a graph here, well I would say I gave a fixed amount of drug right - a certain amount

and it goes into our systemic circulation so this is let's say our blood volume or plasma volume

and it has nowhere to go. There's no exit.

So,I'm going to get a set concentration and because the mass is set (how much drug) and the volume is set

and it doesn't go anywhere. So I just get a graph that is pretty boring.

It's a straight line all the way across

and there is no elimination so this is a straight line.

Now I really can't do it like this. I need to actually see some numbers.

So numbers help me. I think they actually help everybody.

So let's start off by figuring out - Let's figure out the plasma drug concentration.

So in order to figure that out, I need to know what was the total mass of drug I gave and the total plasma volume.

So first off, let's say I gave 10 cc.

So 10 cc means that the volume total was equal to 10 ml.

Now that doesn't mean anything to me because in order to figure out how much drug I gave, I need to figure out the mass.

So volume x concentration = mass.

So let's give you a concentration.

Let's say the concentration of drug in this syringe is let's say is 1 mg/ml.

While using this, I can now figure out the amount of drug I gave.

So the volume in the needle is 10 ml. The concentration in the needle is 1 mg/ml.

And so just by looking at this, if I multiply these two numbers together.

Milliliters will cancel out and I get the amount of drug given a.k.a. the mass.

And so I do that and I see I gave 10 mg of this drug.

So the mass is equal to 10 mg.

Now, remember from that last slide, we had blood which is about 5 L and plasma which was the blood minus the cells which is equal to 2.5 L.

So if I want to figure out the plasma concentration - plasma concentration and the brackets indicate concentration.

Remember concentration is equal to what?

Mass over volume. Mass is the amount of drug I gave which is 10 mg and the volume is equal to 2.5 L.

So, in the last question we remember that is 4 mg/L and that would be what we have here.

And again remember, I gave this injection at Time (T=0) and we assume that it all gets absorbed into our plasma.

Now what we're going to do is we're going to look at something and we're going to come back to it in a little bit.

What we're going to look at is the area underneath this curve.

So to do that, let's give you some values here.

Let's just say this is a total of 4 hours time.

If I was going to calculate the area underneath this curve, I would say the AUC IV.

And why is the area underneath the curve important?

It gives us a sense of how much of this drug we absorbed.

So I would have 4 mg/L here because this is just the rectangle and about 4 hours went by and I would get something about 16.

So let's keep that in the back of our head.

One last thing. In your book or in other books, they might not write this as plasma.

They might actually write this as serum. Really, there's very little difference between plasma and serum.

Serum is just plasma minus the clotting factors and the common clotting factor you know referred to as fibrinogen.

Just remember serum is plasma minus the clotting factors.

So this is IV bolus we gave. 10 mg total. Let's take this exact same 10 mg and instead of giving it IV, let's give it PO or by mouth

So, here is our second case and it is our second easiest case we can deal with.

We're giving the same amount of drug PO and so PO means per os.

Os means mouth or opening like the cervical os.

And so another way you can think of this is per oral or by mouth.

It's still going into one compartment, no distribution and again, we assume no elimination.

So we start off by administering this drug. We gave 10 mg by mouth and we want to get this drug into our systemic circulation.

But unlike before that we can directly inject it to the systemic circulation, we have to swallow the pill.

So what are the process? What's the process as we swallow this pill?

Well first it needs to go into our stomach and it churns with all that stomach acid

and eventually, it works its way through our duodenum and into our intestines.

And in this process though, we might lose a little bit of the drug.

Think we have all this stomach acid, yada, yada, yada.

Now it's in our intestines and it needs to cross our enterocytes

go through our you know intestinal circulation - our superior mesenteric vein, inferior mesenteric vein, portal vein to get into our liver

and again, we might lose a little bit more drug here.

So let's just write you'll lose some drug.

How much drug do we lose?

Let's say from the stomach to the intestine, I'm just making up numbers here.

We lost 2.5 mg and as we're going from our intestines to the liver, we lost another 2 mg

and from our liver, it needs to get into our hepatic vein to the IVC.

Once it's in our IVC, it's in our systemic circulation.

And even here, let's say, we lost another you know 0.5 mg.

If I add these up 2.5, 2, another 0.5. In total, I just lost 5 mg of drug.

So that's important to remember.

So now let's draw a graph and we're going to put plasma drug concentration on the Y axis like we did in the past

and we're going to put the time on the X axis.

So if lost 5 mg and I started with 10, how much do I have left?

5.

So now my plasma drug concentration is just the 5 mg remaining and the plasma volume is 2.5 L.

And so, this concentration is equal to 2 mg/L.

So we can see right off the bat that the maximum concentration that we can get is 2 mg/L whereas before we had 4 mg/L.

So if this was 4, let's say this here is 2.

So that's one component and that is that we actual less drug or a lower plasma concentration because we have less total drug.

The other factor we need to consider is that is actually takes time.

So if this was T=0. By the time we get to T=1 here, this does occur, it doesn't all occur instantaneously.

So if I was going to draw this graph, I might get something that looks something like that.

And so, the process of going from before our plasma ciculation to our plasma circulation, this is our absorption.

Remember, absorption is the process of the drug getting into our systemic circulation.

Now let's look at the area underneath this curve.

And let's just assume this is our rectangle again.

So if this is 4 hours, well I have 2 on this side, 4 on that side

and remember, I don't absorb it but I have this kind of curve going up.

So I'm probably a little bit less than 8 hours or 8.

So If I was going to write the area underneath the curve PO. It's probably around 8. Maybe a little bit less than that.

And so I can write here. Let's write it right here that the area underneath the curve PO we now know is now less than the area underneath the curve IV.

Now this just means that I've absorbed less total drug by mouth than I have IV and that's what the area under the curve tells us.

But we don't use this representation and there's a term that we use that defines the fraction of drug that gets absorbed into our systemic circulation.

and that term my friends is bioavailability.

And so what bioavailability is, is in this scenario, is the area underneath the curve PO divided by the area underneath the curve IV.

And so we're going to talk about this more in detail on the next slide

but remember that this gives us the fraction of the amount of drug that gets into our systemic circulation.

And it's a fraction in relation to how much we've gotten in if we gave it IV.

So remember this term, it's huge.

So before we jump into bioavailability, here are 4 stop, think and repeat questions.

If you want, press pause and answer these questions before moving on.

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