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  • 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.

  • Subtitles by the Amara.org community

Alright people welcome back!

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薬物吸収の概要-薬理学講義2 (Drug Absorption Overview - Pharmacology Lect 2)

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    Yu Syuan Luo に公開 2021 年 01 月 14 日
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