First Pass Metabolism – Elimination Kinetics

00:01 Let's talk about a concept called first pass metabolism. Let's take a look at how a drug enters into the body.

00:09 So that oral drug is ingested and it goes into the stomach. From the stomach, it goes into the small bowel, and then to the large bowel, and then eventually is eliminated into the feces through the colon.

00:21 What happens when that drug goes into the liver? So, through the portal circulation, the drug will enter into the liver. It may or may not get processed or cleared, and then it get dumps back into the bowel through the bile. Now, enterohepatic circulation is a different concept because now instead of having the drug being just simply eliminated through the bile from the bowel, it goes into the bile, and when it's in the bile, it gets reabsorbed through the portal circulation and goes back to the liver. So that circular motion of the drug between liver and small bowel refers to enterohepatic circulation. Drug cycle between intestine and liver.

01:06 First pass metabolism is an important concept when we talk about clearance.

01:12 So, clearance is the rate of elimination divided by the plasma concentration.

01:17 It's going to be proportional to drug kinetics, to blood flow, and to the condition of the organ itself.

01:24 I want to also discuss something called flow limited clearance. So, here we have a picture of the kidneys.

01:29 The kidneys are a classic example of flow limited clearance. Remember that we have about 180 litres of blood pumping through that kidney every single day. If you cut that flow in half, the ability of the kidney to clear drugs is reduced by half, or at least the maximal amount.

01:48 So the kidney is a classic example of flow limited clearance.