Drug Distribution – Absorption and Distribution | Pharmacokinetics (PK)

by Pravin Shukle, MD
(1)

My Notes
• Required.
Learning Material 2
• PDF
Slides Pharmacokinetics Pharmacology.pdf
• PDF
Report mistake
Transcript

00:01 Here is a case study, compound C. A 25 year old takes compound C. Levels were measured and found to be 300ng/ml.

00:11 The volume of distribution is 100L. How much C was ingested? Okay so this is an interesting question because we start to introduce concepts of volume of distribution. The answers here are clearly somehow calculated and give you an answer with a 3 in it. The qestion is, what is the answer. Okay, what's the volume of distribution. The volume of distribution is the amount of drug in the body divided by the concentration in the blood. Now that sounds kind of complicated but let me explain it to you with some pictures. So let's take a look at drug A. We put drug A into the blood and after it diffuses across various membranes, you have 2 units of drug A in the blood or the vascular compartment.

00:59 And you have 18 units of drug A in the extravascular compartments. Let's say it's in the tissues or in the interstitial tissues. Okay, what's the volume of distribution here? Well there is 2 units in the blood and there is 20 units overall. So the volume of distribution is 20 divided by 2 or 10. It's in litres so it's 10L. So, when you think about it it's as if you have 10L of blood. You and I both know that we each have 6L or 7L of blood in our body. But it's as if with the way that the drug is moving that we have 10L of blood. Okay, let's take a look at drug B. This is a different kind of a drug because now it's being bound to a blood protein. You can see that it's all almost all in the blood compartment bound to a protein. The fact that it's bound to a protein is kind of irrelevant here. Only 2 units are in the extravascular tissues. So what's the volume of distribution? Once again, it's 20 divided by 18 which is 1.1. So now, it's as if you only have 1.1L of blood. So the volume of distribution is 1.1L. What about drug C? So now we have drug C. 2 units are in the blood and 198 units are in the extravascular tissues. The volume of distribution is 100 because it's 200 divided by 2.

02:30 So the higher the volume of distribution the more tissue bounded is or the more it's in the tissues. Let's talk about the determinants of distribution of a drug in the body. It's going to be proportional to a number of things.

02:43 First it's going to be proportional to the size of the organ. It's going to be proportional to blood flow.

02:48 It's going to be proportional to solubility and it's going to be proportional to how much it binds. So it could be binding to a protein, it could be binding to a cell membrane, it could even be binding to bone. So it depends on each drug.

03:02 So we talked about compound C sometime ago. We talked about this 25 year old who takes compound C, the levels were measured and found to be 300ng/ml. The volume of distribution is 100L and how much C was ingested? Now you know why this calculation why this number is so important. So let's do the calculation. So the volume of distribution is equivalent to the amount divided by the concentration. So here we have, then we move concentration over so we move it from the denominator into the numerator. So the volume of distribution times the concentration gives you the amount that was ingested. 100L times 300ng/ml.

03:48 Well you have to convert that to mL so it's 100000mL times 300 ng/mL. The mL cancel out. So you get 30000000ng or 30000ug or 30mg. So when we go to our answer we can see that there is a 30mg there and that's the one that we are going to choose.

04:11 So you can see that you are going to need to use math on your USMLE exam when you are answering some of this questions.

04:17 Sorry about that. Let's try another question. Here is a sick women in the intensive care unit. A women has a resistant septic infection with a bacteria that is highly sensitive to vancomycin. The volume of distribution of vancomycin is 0.7L/kg. The patient weight 73kg. How much drug should we give in order to achieve a concentration of 20ug/mL. Okay.

04:46 So we've added something here. We have added volumme of distribution per kilo. So remember in this case we have to multiply it by the patient weight. Let's do that. We have volume of distribution times the kg where the weight of the patient equals the amount over the concentration. So we do the same calculation and you can see on your own that you get 51.83L times 20. And our answer is going to be 1g.

The lecture Drug Distribution – Absorption and Distribution | Pharmacokinetics (PK) by Pravin Shukle, MD is from the course Pharmacokinetics and Pharmacodynamics. It contains the following chapters:

• Distribution of Drugs
• Case Study: Sick woman in the ICU

Included Quiz Questions

1. 400 mg/l
2. 40 mg/l
3. 25 mg/l
4. 2.5 g/l
1. 0.2 mg/ml
2. 1 g/litre
3. 50 g/litre
4. 50 mg/litre
2. Size of the target organ
3. Blood flow
4. Solubility
5. Binding to proteins
1. Increased binding to plasma proteins.
2. All of the choices will decrease the volume of distribution.
3. Increased blood flow.
4. Increased binding to fat.
5. Decreased drug solubility.

Customer reviews

(1)
5,0 of 5 stars
 5 Stars 5 4 Stars 0 3 Stars 0 2 Stars 0 1  Star 0