Name: 藥品流通概述-藥理學講座4 (Drug Distribution Overview - Pharmacology Lect 4)
Uploaded: 2021-01-14T04:43:18.000Z
Duration: 16 min 22 s
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未來進行式

Let's jump in to section 3 here where we'll be talking about distribution and something called the apparent volume of distribution

程度副詞

and I just want to underline this word apparent right now and we'll come back to that in a little bit.

So, like we always do, let's start with a little review.

And so here we're dealing with pharmacokinetics still

and remember that the definition of pharmacokinetics was the change in drug concentration as that drug moves

through the different compartments of your body.

And so, there were 4 components of pharmacokinetics.

Well, we had an acronym that we used A.D.M.E.

A being for Absorption, D for Distribution, M for Metabolism and E being for Excretion.

and today, what we're going to do is focus on distribution.

Before we go any further though, we have to remember the core concepts that we have covered in the past.

So, what was the most important concept that I had you remember?

Well, hopefully you're saying that concentration is equal to mass over volume.

And so, in the past, when we dealt with absorption, we were really kind of just focused on this concept of mass.

We assumed a fix volume and we said you know how does the mass change as this drug gets into your body?

And we defined something called bioavailability.

And so, the way the practical definition of bioavailability was if I gave a certain amount of drug let's say by mouth,

how much of that drug ends up getting into the systemic circulation?

And the way we can figure that out is by using bioavailability.

And we said the actual absorbed mass was equal to the total mass administered x the bioavailability of the route in which we administered that drug.

So it gives us the fraction of drug that is getting into the systemic circulation.

Now remember here that if I gave this drug IV, if this is IV, what's the bioavailability by definition of anything given IV?

and so what that meant was the total mass that you administer IV is the total mass that gets absorbed or that gets into the systemic circulation

because when you give it IV, you're directly injecting it into the systemic circulation

but this is old news. You know this stuff already.

So, in the past we assume that the volume really didn't change

And that we gave the drug and it went into the plasma and it didn't go anywhere else.

But now, we're talking about distribution.

So, volume is the key term when we think of distribution.

Distribution is the dispersion of the drug throughout your body

and the way I like to think about this is that the drug is going from one place to another.

So where does it start? What's the one place?

And so when we think of distribution, if this is a vessel and we took all the cells out of this vessel, out of the blood

So if we started in the vascular space and I had a drug. The process of it going from this vascular space to the extravascular space is what we call distribution.

And remember that this extravascular space now is another volume we need to consider

and that's why we're dealing with volume here.

So what are some examples of the extravascular space where there might be fluids or places that drugs can get into.

Well, we have our interstitial space right?

Well drugs can get into the fat. Drugs can get into the muscle.

And really because drugs are really getting you know we're looking at the water compartments of the body.

Well, remember that plasma was the blood minus the cells.

So, sometimes the intracellular space is associated with extravascular space.

So the cells inside the cells of the fat or inside the cells of the muscles, we know that we have water in those too.

So I'm just going to write here intracellular.

And so, these are all places that the drug can go outside of the plasma and these have a volume

and we need to consider it if we're going to figure out the plasma drug concentration.

So, before we jump into distribution, there's one more thing we want to cover

and that is just to quickly review this case that we had done in the past

and what we're going to do is differentiate this case which had no distribution from the next case which does have distribution.

We gave 10mg of a drug IV bolus but in the past, we assume that that drug stayed in only 1 compartment

So here, we were assuming no distribution and just to have a really simple model, we also assumed no elimination.

So, I gave 10mg of drug. Here is my syringe right and here I have 10mg

and what I always want to do when I'm thinking of pharmacokinetics is figure out the plasma drug concentration.

So, we remember our most important concept: concentration is equal to mass divided by volume.

And so, because we only assumed one compartment, I said the mass was 10mg.

That was the amount of drug absorbed and administered because I gave it IV divided by the plasma volume

because we're trying to find the plasma concentration of 2.5L and if I solve for that, I get a concentration equal to 4mg/L

and because this drug is not distributing anywhere else and there is no elimination,

I know that from beginning to end, my plasma  drug concentration is essentially 4mg/L all the way through.

So in the next case here which will be case 3 because we've already done case 2 when we considered IV administration of a drug

In the next case, we're going to look at distribution and we're going to assume a multi-compartment model.

So, the in case 3, drugs getting into and around our body.

So we have an IV bolus and let's just assume we're still giving this 10mg

and now we say there's multi-compartments. We have our plasma compartment and we have our extravascular compartment.

So we start off and say okay, I'm going to administer 10mg of a drug IV bolus and let's draw out these comparments.

And so, if I was going to visually represent them, I could say all right I would have my plasma space here or my vascular space here

and then I have my extravascular space here.

Now, we need to remember that this isn't you  know fluid you know continuum.

There's something separating the vascular space from the extravascular space

and hopefully, you're telling me that that thing is separating is a vascular endothelium.

And so that's what this green guy here represents and so I say, Oh I have a vascular endothelium.

And so, what we're going to consider like we always do with pharmacokinetics is if I administer this 10mg of drug IV bolus,

what happens to the plasma concentration with time as this drug is moving through the different compartments of the body?

So, what do we always do first, before we graph anything, before we do any pharmacokinetics question,

we always remember concentration is mass over volume.

That is always the first thing that you should go to no matter what.

And so, now I need to figure out what's going on.

So, let's just you know think okay, I've got a syringe

right I guess the syringe isn't as pretty as the other one.