Drug Clearance Overview and Pathways

A measure of the body's ability to remove a drug from plasma. It is a model-independent parameter, meaning it doesn't rely on specific mathematical models.

A major pathway for drug removal from the body. The liver metabolizes drugs to make them easier to excrete.

Another major pathway for drug removal from the body. The kidneys filter waste products, including drugs, from the blood.

A third major pathway for drug removal, particularly for certain types of drugs. The bile helps excrete these drugs.

Clearance and volume of distribution are independent parameters, meaning a change in one does not affect the other.

Clearance, along with volume of distribution, determines the rate at which a drug is eliminated from the body. A high clearance means the drug is eliminated quickly.

The time it takes for the drug concentration in the body to decrease by half. It is influenced by both clearance and volume of distribution.

The sum of all clearance processes, including liver metabolism, kidney filtration, and biliary excretion.

The process of modifying a drug molecule through oxidation, reduction, or hydrolysis.

Involves adding a functional group to a drug molecule or its metabolite.

Enzymes that catalyze oxidation reactions in drug metabolism.

A process where a drug's activity is reduced or lost after metabolism.

A drug that requires metabolism to become active.

Changes in drug metabolism due to factors like age, liver disease, or genetics.

A state where the activity of metabolic enzymes is reduced.

A state where the activity of metabolic enzymes is increased.

Drugs with a narrow range between effective and toxic doses.

Databases that provide information on potential drug interactions.

Changes in enzyme activity due to genetic differences across populations or individuals.

The rate at which the body eliminates a drug or metabolite.

The time it takes for the concentration of a drug or metabolite to decrease by half.

A scenario where the metabolite has a longer half-life than the parent drug.

A scenario where the metabolite has a shorter half-life than the parent drug.

The volume of blood that the liver clears of a drug per unit time. It represents the efficiency of the liver in eliminating a drug from the body.

The fraction of the drug that is metabolized by the liver during a single pass through the organ. It indicates the liver's effectiveness in removing the drug.

The process of removing a drug from the body, involving metabolism and excretion.

The volume of fluid in which a drug is distributed throughout the body. It reflects the drug's tendency to stay in the bloodstream or distribute into tissues.

The area under the curve of the drug concentration versus time plot. It represents the total amount of drug exposure over time.

The maximum concentration of the drug in the bloodstream after administration.

The time it takes to reach the peak concentration after administration.

The rate at which the drug is eliminated from the body, independent of the volume of distribution. It reflects the intrinsic capacity of the body to remove the drug.

The process of converting a drug into a different form, often to make it less active or easier to excrete.

The percentage of the administered drug that reaches the systemic circulation after oral administration. It reflects the extent of drug absorption and first-pass metabolism.

The phenomenon where a drug is metabolized in the gut wall and liver before reaching the systemic circulation, reducing its bioavailability.

The ability of a drug to bind to plasma proteins, reducing its free concentration and affecting its distribution and elimination.

The intrinsic ability of the liver to metabolize a drug, independent of blood flow.

The rate at which a drug is eliminated from the body, often measured in volume of blood cleared per unit of time.

The amount of drug eliminated per unit of time.

A mathematical model describing how the liver clears drugs, assuming a well-mixed environment.

The rate of metabolism or extraction is the amount of drug eliminated per unit of time.

The extraction ratio is the fraction of drug removed from the blood as it passes through the liver.

The absolute rate of drug metabolism by liver enzymes, independent of blood flow.

A drug with a high extraction ratio, meaning most of the drug is metabolized by the liver.

A drug with a low extraction ratio, meaning only a small amount of the drug is metabolized by the liver.

The maximum rate of drug metabolism by an enzyme.

The drug concentration at which the enzyme is operating at half its maximum rate.

The fraction of unbound drug in plasma.

The rate at which drug is presented to the liver, calculated as blood flow times incoming drug concentration.

The ability of a drug to cross cell membranes, typically relating to its lipid solubility.

The fraction of a drug that reaches systemic circulation after oral administration.

The relationship between oral bioavailability (F) and extraction ratio (E) is often expressed as F = 1 - E.

The amount of drug surviving the first-pass effect depends on the activity of liver enzymes, liver blood flow rate, and the fraction of unbound drug.

For high extraction drugs, a small change in liver blood flow, fraction unbound, or intrinsic clearance can significantly impact oral bioavailability.

For low extraction drugs, oral bioavailability is close to 1 (or 100%), meaning most of the drug reaches systemic circulation.

Hepatic clearance for high extraction drugs is primarily dependent on liver blood flow, while for low extraction drugs it's dependent on the fraction unbound and intrinsic clearance.

Theophylline is a low extraction drug, meaning it has high oral bioavailability and is primarily cleared by hepatic enzymes. Cimetidine is a P450-3A inhibitor, which can reduce Theophylline clearance and lead to its accumulation.

Drugs with high molecular weight (greater than 250 g/mol) and polar compounds are often eliminated via biliary excretion.

The amount of blood that flows through the liver per unit time. This is important for high extraction drugs, but not for low extraction drugs.

For low extraction drugs, the liver's ability to remove the drug primarily depends on the fraction unbound (fu) and the intrinsic clearance. Changes in liver blood flow don't significantly affect clearance for these drugs.

The fraction of a drug that reaches the systemic circulation after being administered orally, considering the first-pass effect. It indicates how much drug is available to exert its therapeutic effect.

For low extraction drugs, an increase in the fraction unbound (fu) will increase the clearance because more drug molecules are available for metabolism. However, this doesn't mean the drug is being metabolized at a faster rate - it's just that more drug molecules are available to encounter the enzymes.

For low extraction drugs, an increase in intrinsic clearance will increase the hepatic clearance because the liver enzymes are metabolizing more drug molecules per unit time. Even though the overall rate of metabolism is still slow, the increased enzyme activity results in more drug removal.

For low extraction drugs, the effect of liver blood flow on clearance is minimal. This is because the rate of drug metabolism is very slow, and even with increased blood flow, the same percentage of drug will be metabolized.

When a drug is metabolized primarily in the liver, the rate of metabolism is often influenced by the fraction unbound (fu) and the intrinsic clearance, as much of the drug is free to reach the liver enzymes.

Low extraction drugs exhibit a small extraction ratio because only a small amount of the drug is metabolized in the liver. This means that most of the drug passes through the liver unchanged.

Low extraction drugs have a lower clearance than high extraction drugs, due to the slow rate of drug metabolism. This means that the drug will remain in the body for a longer period of time.