How is hepatic clearance measured?
Hepatic clearance is determined by hepatic blood flow (Q), free or unbound fraction (fu), and intrinsic hepatic clearance (CLint). Changes in protein binding generally do not alter steady state free concentration of drug if intrinsic hepatic clearance is unchanged.
What does liver clearance mean?
Description. Hepatic clearance quantifies the loss of drug during its passage through the liver. Hepatic clearance results from hepatic metabolism and biliary excretion and is a function of the hepatic blood flow, the drug plasma protein binding and the activity of liver enzymes and transporters.
What are the units for clearance?
The units of clearance, like those of flow, are volume per unit time. Therefore, clearance represents that volume of blood (or plasma) from which the drug has been completely removed per unit time. For example, if drug concentration is 10 μg/ml and clearance is 100 ml/min, the rate of drug elimination is 1000 μg/min.
What is the unit of total clearance?
Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration. Excretion, on the other hand, is a measurement of the amount of a substance removed from the body per unit time (e.g., mg/min, μg/min, etc.).
How is drug clearance measured?
[1] Thus, the unit of measurement for drug clearance is volume/time. Another equation can calculate clearance. Clearance is equal to the rate at which a drug is removed from plasma(mg/min) divided by the concentration of that drug in the plasma (mg/mL).
How is blood clearance calculated?
It can be measured in a single organ by sampling drug concentration in the arterial blood into (Cin) and venous blood from (Cout) the organ. Thus if the arterial blood contains 15 mg/L of drug “A” and venous blood from the organ contains 9 mg/L, the ER is (15-9)/15 = 6/15 = 0.4.
How do you calculate clearance?
Another equation can calculate clearance. Clearance is equal to the rate at which a drug is removed from plasma(mg/min) divided by the concentration of that drug in the plasma (mg/mL).
What is hepatic clearance and how is it calculated?
Hepatic clearance (CLH) may be defined as the volume of blood perfusing the liver that is cleared of drug per unit time. Usually, hepatic clearance is equated with non-renal clearance and is calculated as total body clearance ( CLE) minus renal clearance ( CLR ).
What is the hepatic clearance of phenytoin?
The hepatic clearance of phenytoin, a restrictively eliminated drug that is predominantly a CYP2C9 substrate, increases during pregnancy, resulting in correspondingly lower total plasma concentrations [62].
What are the two major determinants of hepatic clearance?
The two major determinants of hepatic clearance are hepatic extraction ratio and hepatic blood flow Hepatic extraction ratio is the fraction of the drug entering the liver in the blood which is irreversibly removed (extracted) during one pass of the blood through the liver.
What is the difference between hepatic clearance and intrinsic clearance?
As the hepatic clearance becomes closer to hepatic blood flow, the clearance is more independent of metabolic (intrinsic) clearance consisting of unbound fractions (in blood/microsomal incubation mixture) and intrinsic clearance for unbound form.