Name: Drug Bioavailability Overview - Pharmacology Lect 3
Uploaded: 2013-10-25T09:16:20.000Z
Duration: 16 min 45 s
Description: Thousands of YouTube videos with English-Chinese subtitles! Now you can learn to understand native speakers, expand your vocabulary, and improve your pronunciation...

And so the definition of bioavailability is the fraction of the administered dose that reaches the systemic circulation.

So, how much of that dose is getting into my systemic circulation?

Well, what does the bioavailability depend on?

First, it depends on the properties of the drug. Some drugs are very easily absorbed, other drugs are not easily absorbed.

So the higher the absorption rate of the drug, the higher the bioavailability.

The other thing that bioavailability depends on is the route of administration.

Like we said before, if I give something intravenously, 100% of that drug is getting absorbed into the plasma.

All of the mass that was in that needle is the mass that's in the systemic circulation.

But if I give a drug PO or by mouth, all of that drug is not getting into the systemic circulation

and therefore, will have a decreased bioavailability.

Well, the first equation is somewhat conceptual and this has us use those graphs that we kind of drew out when we were first talking about absorption.

And so, what's going on here is the bioavailability of a particular route of administration is equal to the area under the curve via that route of administration

divided by the area under the curve had I given that drug IV.

And so, when I say the area under the curve really if you remember before, we had time here and the plasma concentration here

and so, let's just use the example we had last time.

I gave a drug IV, there was no distribution or elimination.

I kind of had a graph that looks like this. This would be the area underneath the curve.

Let's say this is IV and this is our hypothetical situation.

Whereas had I given that drug PO, the area under the curve would be decreased.

AUC - so the area underneath the curve is proportional to the amount of drug absorbed.

First off, bioavailability is a fraction. And so, because it's a fraction, oftentimes you'll see this written as F.

So if I was going to say the bioavailability of a drug given PO. Let's switch back to - let's use blue.

So, the bioavailability PO is equal to the AUC PO.

We've already said it but it's the if I gave a certain mass of drug by mouth, how much of that drug is getting into the systemic circulation?

In other words, if I gave that same drug intravenously, how much of that drug would have gotten into my systemic circulation?

So this definition is a little conceptual. We're going to make it a little more practical as we develop this concept.

So what are some practical key points that allow us to really use this definition of bioavailability

because I highly, highly doubt that you'll ever be measuring an area underneath the curve of a graph unless you're doing some sort of pharmacokinetic study.

First off, let's look at what area underneath the curve IV really means.

So you can think of the area underneath the curve IV as the amount of drug in the plasma if 100% had been absorbed.

In other words, this here is the total mass of the drug - the total mass of the drug administered.

Think of this as the actual dose. I'm giving this much drug and if we assumed all of it had been absorbed, that's actually the total mass that everything was there

and then think of the area underneath the curve PO as the actual amount of drug that gets into the plasma.

So, another way we could write this is the mass after absorption.

whereas the AUC IV, you can think of this as before absorption.

So if I was going to put this all together, I'm just going to reiterate this point because it is hugely important

and the AUC IV is the total mas given or the total mass administered.

And so, which one is before absorption? Which one is after absorption?

The mass in the plasma is obviously after absorption because absorption is the process  for which a substance gets into the circulation.

All right, we've hammered this down. Let's do a problem and make sure you get it.

Metoprolol is a drug that works on the heart. The oral bioavailability is 50%.

If the standard IV dose is 50mg, what should the oral dose be?

Now I can almost guarantee you that you're going to get some permutation of this question on a major exam.

So you must know this concept so let's work our way through it.

Here's a quick assumption just to help. Assume our goal is to reach the same plasma drug concentration in both cases.

So let's think about this the way a student might think about it.

So, we're going to go through 2 separate methods. One of them is going to be correct, the other one is going to be incorrect.

So if I was a student and I saw this problem, I would first just jot down the things that I knew.

I would say the bioavailability PO is 50% or 0.5. I'm not really sure what I should do with these yet so let's continue.

So I might take the equation for bioavailability and say all right, I know the bioavailability here is 0.5,

the area underneath the curve for a particular route of administration divided by the AUC IV

and I know something about IV here so, from my perspective I know what this is, I know what this is and I'm trying to solve for that.

So I go through and solve for the AUC route and we know this route that I'm looking for is the oral dose, so that's PO.

And so, if I rearrange this equation, I get something like - if I just took this and brought it up there,

I get the area underneath the curve by mouth or the amount of drug that gets absorbed into the plasma circulation if I took that drug by mouth

is equal to the AUC IV x the bioavailability.

So, I look at this. I know something IV is 50mg. So I write 50mg here.

I multiply this by the bioavailability of 0.5.

And so, if I do this, I would get an answer of 25 mg

and hopefully, you can tell me that this is actually wrong.

Now, the answer means something but it's not what we were looking for.

We're trying to figure out what the oral dose should be.

Is the oral dose that we're looking for the dose before absorption or the dose after absorption

or is it the amount of drug before absorption or the amount of drug after absorption.

We're trying to figure out the amount of drug we should give before absorption or the total mass of the drug that should be administered.

So, really what I found here is not what the oral dose should be.

Here, we unfortunately made the assumption that the oral dose was 50 mg and if it had a bioavailability of 0.5, how much would end up in my plasma?

And so, what I did is I wrote it down here in kind of a paragraph form.

If I administered a dose with a total mass of 50 mg PO. After absorption, I would only actually have 25 mg in my plasma.

So remember, just to jump back to our last slide, the AUC PO right is the actual mass in plasma.

This is after absorption vs. the AUC IV is the total mass administered - this is before absorption.

So AUC PO, this is the actual mass in the plasma.

This guy right here was our dose administered so to speak. That's the total mass given.

And we know this guy right here was just the bioavailability.

So this is actually the useful equation that we should use.

Before, I was saying kind of saying there was a conceptual way of using bioavailability with AUCs but really, there's a practical way.

And so now, let's get to the practical method.

And so, before we go any further, the approach here was wrong.

Let me switch colors to red. It is wrong!

(singing) If loving you was wrong, I don't want to be right...

So, what I did here is I just took this equation that we kind of just figured out the practical equation so to speak for bioavailability