Table of Contents
- 1 Can hepatic clearance exceed liver blood flow?
- 2 How does hepatic blood flow affect metabolism?
- 3 What affects hepatic clearance?
- 4 What is a high hepatic extraction ratio?
- 5 How would the first pass effect be affected in a person with liver damage?
- 6 How does ascites affect volume of distribution?
- 7 How does intrinsic clearance affect total hepatic clearance?
- 8 What happens to hepatic clearance with increased blood flow?
Can hepatic clearance exceed liver blood flow?
2 Hepatic Clearance It is obvious that the ClH cannot exceed the total volume of blood reaching the liver per unit of time, that is, the liver blood flow Q. The ratio of the ClH of a drug to the hepatic blood flow is called the extraction ratio of the drug (E).
How does hepatic blood flow affect metabolism?
The hepatic arterial flow does not change in response to altered hepatic metabolic activity as shown by the lack of expected vascular changes with altered oxygen content of blood, altered metabolic activity induced by enzyme induction or enzyme inhibition, and altered oxygen uptake or biliary secretion.
What is hepatic drug clearance?
Hepatic drug clearance can be defined as the volume of blood perfusing the liver that is cleared of the drug per unit of time. There are three major parameters that determine drug elimination by the liver: blood flow through the liver (Q), which reflects drug delivery to the liver.
How does liver disease affect clearance?
Liver dysfunction may not only reduce the plasma clearance of a number of drugs eliminated by biotransformation and/or biliary excretion, but it can also affect plasma protein binding which in turn could influence the processes of distribution and elimination.
What affects hepatic clearance?
The two major determinants of hepatic clearance are the efficiency of drug removal from the blood and the efficiency of blood delivery to the liver. The former is described by the hepatic extraction ratio, and the latter is simply the blood flow to the liver.
What is a high hepatic extraction ratio?
It is defined as the fraction of drug removed from blood by the liver, and depends on 3 factors— the hepatic blood flow, the uptake into the hepatocytes, and the enzyme metabolic capacity. Examples of drugs with a high hepatic extraction ratio include propranolol, opiates, and lignocaine.
What is hepatic blood flow?
Hepatic blood flow and hepatic pressures Total hepatic blood flow ranges between 800 and 1200 mL/min, which is equivalent to approximately 100 mL/min per 100 g liver wet weight. Although the liver mass constitutes only 2.5% of the total body weight, the liver receives nearly 25% of the cardiac output.
How is hepatic bioavailability calculated?
The maximal predicted oral bioavailability (F) is given by the product of the fractional hepatic clearance (fH), which is 1 minus the hepatic extraction ratio EH (1−0.8=0.2) and the fractional oral absorption (fo), assumed in this case to be unity (maximal case). Therefore, F=0.2×1=0.2.
How would the first pass effect be affected in a person with liver damage?
The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus may greatly reduce the bioavailability of the drug.
How does ascites affect volume of distribution?
In normal subjects and patients without ascites the volume of distribution increased with decreases in protein binding. Ascites was associated with a further increase in the volume of distribution.
How many folds change in hepatic clearance?
However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice logical changes affecting the circulation.
What is hepatic extraction ratio?
The fraction of drug presented to the liver that is eliminated during a single pass is called the hepatic extraction ratio. The hepatic extraction ratio becomes equal to 1 (unity) when the drug that reaches the liver is completely eliminated. When no drug is eliminated by the liver, the extraction ratio is zero.
How does intrinsic clearance affect total hepatic clearance?
Increasing the intrinsic clearance will have diminishing effect on total hepatic clearance The rate of blood flow to the liver determines the rate of drug delivery to the liver, and therefore the net hepatic clearance of the drug depends on blood flow.
What happens to hepatic clearance with increased blood flow?
Hepatic extraction ratio will drop more rapidly with increasing hepatic blood flow Hepatic clearance will not increase significantly with increasing blood flow Hepatic clearance will increase in a fairly linear fashion, in proportion to hepatic blood flow Increasing the intrinsic clearance will have diminishing effect on total hepatic clearance
How is hepatic clearance described in the well stirred model?
Hepatic clearance in the well-stirred model is described by: where QH is the liver blood flow, fu,b is the fraction unbound in the blood, and CL int (the intrinsic clearance) is a measure of the maximal ability of the liver to metabolize a drug in the absence of protein binding or blood flow limitations.
How does the hepatic extraction ratio affect drug clearance?
An increase in the fraction of unbound drug (f) will increase clearance, and a decrease in unbound drug will decrease clearance. Intermediate extraction ratio. Hepatic clearance of these drugs is dependent on both hepatic blood flow, intrinsic metabolising capacity of the liver and the free drug fraction.