Hello everyone, it's Jessica again and welcome to CritIC, the pharmacokinetics series! Before we talk about metabolism and excretion, I'd like to explain the concept of clearance in half-life first. After the absorption and distribution of the drug, the body will try to get rid of it. A drug can be cleared in mainly three ways. By metabolism, in which the drug is transformed into an inactive substance that's more water soluble so that it then can be excreted.
By direct excretion, or by a combination of both. The exact processes that happen in the liver and in the kidney are covered in the next videos. In this video, we'll talk about the importance of clearance. Clearance is defined as the amount of plasma from which a substance is completely removed per unit time.
Notice I didn't say amount of drug, but amount of plasma. Its unit is volume per time. not concentration per time, which can be confusing.
See this bucket of water containing 6 drug particles? This volume is cleared by the kidney. Now it has no drug particles. Let's call this clearance 100. See this other bucket of water?
Same amount of water, but now 24 drug particles. This volume is cleared by the kidney as well. Note that the clearance is exactly the same, 100. The amount of drug that's cleared changes, not the volume.
This is what happens in what we call first order kinetics. And since this applies to most drugs, we'll leave it at that for this video. So why is this important? Well, through absorption and distribution, we filled up our body, or bucket, with drug. Now we learn that the body will try to get rid of it through clearance.
If we know the clearance, we know how much to give the patient to maintain certain plasma levels. What goes out must go in again. So clearance is important to calculate maintenance dose.
So how long will it take to get into this steady state? That depends on the drug's half-life, which is a way of bringing the volume of distribution and clearance together. Half-life is defined as the period of time required for the concentration or amount of drug in plasma to be reduced by one half. So assuming we're at steady state, if we discontinue the drug, after one half-life of the drug, 50% will be cleared.
After 2, 75%. After 3, 87.5%. After 4, 93.75%. and after 5 half-lives, 96.875% of the drug will be cleared. This graph can also be flipped.
If we start with nothing, it will take about 5 half-lives before the drug will reach optimal serum concentrations. So half-life can be used to calculate when you'll reach this steady state, and it can also help you to calculate when the drug is cleared from the body. The concept of half-life also helps you to predict what happens to the drug concentration when either clearance or volume of distribution are affected.
For example in renal failure. For a drug that's renally cleared, if renal function halves, half-life is doubles. Note that you do need to know how much of the drug is cleared by the liver and how much is cleared by the kidney.
For example, a drug is cleared by both the liver and kidney for 50% each. This patient then develops renal failure. Let's assume renal clearance is 50% of what it was before.
The liver still does the same amount, but the kidney only does half of 50%, which is 25%. So the clearance of that specific drug is now 75%, or 3 fourths. So the half-life will increase with a factor 4 to 3, which equals an increase of 33%. Depending on the drug, you may want to adjust your dose. Now let's take a look at these steps individually in the next two videos on metabolism and excretion.
And that's it for this video on Clearance and Half-Life. If you like these series, it really does help me if you give them a thumbs up, share them, subscribe to the channel, or drop me a line in the comments section. Thanks!