Alright, good afternoon all, my name is Brookie Best, I am a pharmacist by training. I'm faculty here in the School of Medicine and the School of Pharmacy. And some of the research I do is in the area of Pharmacokinetics. Figuring out how the drug travels through the body and how we need to dose it. And today, I'm going to talk to you about key concepts and drug delivery. So what we're going to talk about today is first something I call ADME, absorption, distribution, metabolism, elimination, which I'll explain in a minute. We'll mention where we can administer drugs, what types of dosage forms are available, and I'll give you some examples. An what delivery systems have been developed. Just as a fair warning this is a very, very, very brief overview of these topics. some of the pharmacy students know, we actually cover these topics in 3 quarters, so a year long course sequence in the pharmacy school. And that, those three quarters of courses have been condensed into about a 45 minute talk. So clearly we're just, I wouldn't even say we're scratching the surface. I'm showing you where the surface is [LAUGH], okay? So, alright. So the first thing is sort of a vocabulary lesson in orienting you to the vocabulary I typically use. there is something called pharmacokinetics. So, Pharmacokinetics, so pharma meaning drug, kinetics meaning rates of processes. How quickly things happen. So, kinetics typically accounts for how the drug travels through the body. And then Pharmacodynamics, the dynamics are the effects that the drug has. So what the drug does to the body, like relieves pain or lowers, lowers blood pressure or lowers cholesterol or something like that. So those are the two broad categories, Pharmacokinetics, Pharmacodynamics. And within kinetics, we have absorption. So you have to give a dose of the drug and it has to be absorbed typically somehow in to your systemic circulation or your bloodstream. Once its in the bloodstream, it has to be distributed to various places in the body, hopefully to the side of action where it will have its desired therapeutic effect. it may also be metabolized, or changed by the body. And at some point it's got a be eliminated, your body has to get rid of it. So there is the absorption, distribution throughout the body, metabolism. And not all drugs are metabolized, that means they're changed. Some drugs are change, some drugs are just eliminated unchanged, in elimination. So I'll go into a little more detail on ADME for absorption. Most of the dosage forms that we give are solid. Like if you consider a pill, right? You take a tablet, you take a capsule, that's a solid dosage form. So the first thing that has to happen is that has to break apart, all right? So that's gotta disintegrate into smaller particles, deaggregate into very fine particles and go into solution. Because once it's dissolved in solution, that's when it can travel and pass through say, the membranes of our GI tract or other membranes of the body to actually get absorbed. Okay. So once it's in solution and that's when your body, it can travel through the body and be absorbed. And, and there's only 1 way to bypass absorption, and that's if you give a drug directly into the bloodstream. Which we can do, we can give people intravenous injections straight into the bloodstream. But any other way we deliver a drug, it has to travel through a membrane at some point to get into the bloodstream. Whether we give it orally, or rectally, or intramuscularly, subcutaneously. it does have to pass through a biological membrane, okay? So, membranes back to basic biology from high school and early college, right? They're bilayers, lipid bilayers. They've got an oily surface and they've got a hydrophilic or watery surface. So, our drugs have to be able to navigate through these various environments. They have to be, you know, hydrophilic or water loving enough to stay dissolved. But it has to also be hydrophobic or, or lipophilic oil loving enough to get through the oily parts of that membrane in order to pass through into the systemic circulation. So, what are some challenges to oral absorption? I'm going to spend a few minutes talking about oral absorption in particular because most drugs are given orally, right? It's the easiest way, patients know what to do to. Just swallow a pill, and it has a very good sort of what's the word, acceptance by patients, okay? So, what are some of the challenges to oral absorption? Well your GI tract, your gastrointestinal tract is really quite complicated. And so drugs have to navigate all of those different environments in your GI tract in order to be absorbed. Some of the challenges include, the varying pH levels throughout your GI tract. Your stomach can be very acidic. Your intestines can be more towards neutral, and your large intestines can even be slightly basic. And so the drug that you get has to be stable to the various conditions it's going to pass through. If acid degrades the drug, then if it sits in the stomach that's very acidic for very long, you're going to be degrading the drug before you have an opportunity to, to absorb it. Alright, it has to be, it has to be able to dissolve. So some drug candidates we look at, tend to be so hydrophobic that they can't go into solution. If they can't dissolve into solution, they're not going to be able to be absorbed, at least to the GI Tract. So, it has to stay dissolved it has to dissolve fast enough that it won't pass all the way through your GI tract and still be you know, trying to dissolve. It has to be permeable to the gut membranes. That means it has to have the right balance of characteristics that it, allow it to pass through, like the, the lining of your intestine, okay? So it has to have the right combination of properties. it has to be stable to your liver, in essence. So when you eat food or you ingest something, and it gets to your intestines. You have this vast surface area, right? These wound up intestines, coiled. And the job of your body is to suck out all the nutrients, absorb all the the proteins, the fats, the vitamins and minerals from your food. And the first place things go when they're absorbed from the intestines is straight to the liver, right? So it comes to the liver first, the liver has a lot of different ways to detoxify whatever you ingested to prevent it from making it through to the bloodstream. Well, your liver might see a drug as a foreign substance or a poison or a toxin, and might try to break apart or break down that drug and prevent it from getting into the blood stream. Okay, so, your drug has to be stable or at least stable enough for some of it to get through the liver to make it into the blood stream. There are some additional factors that effect oral absorption, such as how fast it travels through your GI tract when you are fasting, you haven't eaten and you maybe have a pill with some water. It actually passes through your stomach very rapidly, within a matter of minutes, 10, 15, 20, 30 minutes. It's made it to the intestines. however, if you take a nice, big, fat, greasy meal with your drug, that drug might sit in your stomach now for 2, 3, 4, 5 hours depending on your own body's individual workings. And so that's one thing that will affect how quickly you absorb a drug and maybe how much of the drug you absorb. Some drugs actually need all of that food content and they need to stay in the stomach for awhile to get dissolved. Where as other drugs might be unstable to acid so you don't want them sitting in the stomach very long cause they might get degraded. So its not a good or a bad thing. It really depends on the drugs in terms of how quickly it passes through the stomach, and whether or not it helps or hinders absorption. how quickly it passes through your intestines might effect how well its absorbed. Whether its obtained in the colon or your large intestine can affect how well a drug is absorbed orally. How well your GI track is profused, the blood flow all around your intestines. Your food and diet can affect drug absorption. Sometimes the drug might bind to components in the food, and not be available to be absorbed. let's see what else, disease, or altered anatomy, if you have a gastric bypass, if you have a resection, or removal of some of the intestines. That decreases the surface area available for absorption. So, again, you know, this isn't a comprehensive list and I'm not going to explain every single mechanism that can effect oral absorption. But you start to see that it's not as simple as just putting a chemical into a pill and taking it and assuming it's going to get into the bloodstream. Okay, there are a lot of different things that can effect how much of that drug is actually going to be absorbed when you take it orally.
