Clearance Flashcards
What is clearance? What is it expressed as?
◦ Volume of plasma which contains the total amount of drug that is removed from the body in unit time
- Expressed as volume per unit time
What is clearance values usually used for? What is renal clearance?
- Clearance can assess the excretory capacity of an organ (kidney)
• Renal clearance (Clrenal): the volume of plama containing the amount of drug that is
removed from the body by the kidneys in unit time

What is the formula for total body clearance?
• total clearance = sum of hepatic + renal + other
What are the most important types of clearance? What is the overall clearance of a body called? What is the definition?
Usually renal and hepatic clearance are the most important • The overall clearance of a drug or total body clearance (CLtotal ) is the sum
of clearance rates for each mechanism involved in eliminating the drug
What is clearance used to determine? What does it not determine?
• Determines rate of drug elimination.
• proportionality factor To determine the rate of drug elimination
Clearance does not describe the amount of drug being eliminated.
• Clearance is high, rate of elimination will be high as well.
• Clearance is volume of blood that is clear.
What is the rate of drug elimination? What is the formula?
Rate of drug elimination is the amount of drug being eliminated per unit time
Rate of drug elimination: Cp x CL total
How can overall clearance be determined after a single IV bolus? What is the formula?
The overall clearance CL total
can also be estimated by measuring plasma concentrations at intervals following a single intravenous bolus dose (Q mg
Formula attached:
Explainations for formula:
Where AUC 0 −∞
is the area under the full curve relating Cp to time following a bolus
dose given at time t = 0 • AUC 0 −∞ provides an integrated measure of tissue exposure to the drug in units of
time multiplied by drug concentration

How can overall clearance be determined after a CRI? What is the formula?
Drug clearance can also be determined in an individual subject by measuring the plasma concentration of the drug ( mg/L) at intervals during a constant-rate intravenous infusion (X mg of drug per hour)
Formula attached:
Formula explaination: Where Css is the plama drug concentration at steady state

What happens to the plasma drug concentration over time in each of these scenarios?
CRI administration?
Single Bolus dose?
During a constant intravenous infusion at rate X mg/h, the plasma concentration increases from zero to a steady-state value (C
ss
); when the infusion is stopped, C declines to zero.
Following an intravenous bolus dose (Q mg), the plasma concentration rises abruptly and then declines towards zero.
Concentration declines exponentially.

What is the elimination half life?
Elimination T½ refers to the disapearance of drug from plasma
• Is clinically relevant and the most often reported pharmacokinetic parameter
• It is defined as the time necessary for plasma or blood concentrations to decline by 50%
Fill in the blank:
The more ______ a drug is cleared by an organ, the shorter
the drug half-life
• The longer the half-life, the ______ the drug will_____ in the
body
The more rapidly a drug is cleared by an organ, the shorter
the drug half-life
• The longer the half-life, the longer the drug will persist in the
body
How many half lives must occur for 97 % of the drug to be eliminated?
For example, at one drug half-life, 50% of the dose has been
eliminated; after five T ½s (half-lives) 97% of the drug has
been eliminated
If Vd is low plasma concentration is ________
If Vd is low plasma concentration is high.
What will affect a half life? How does that affect the duration of the drug?
- Any factor that changes VD of a drug will affect its half life
- An increases of Vd can increase the half-life and extend the duration of action of the drug
What does elimination half life, and dosing interval help practicioners determine?
• Elimination half-life along with the dosing interval also determines the amount of drug that accumulates with each dose as steady-state equilibrium is reached
What 2 things should be considered when determining an appropriate dosing interval?
• Along with the therapeutic range, the half-life should be the basis for an appropiate dosing interval
What situations will increase a drugs half life?
◦ Decreased renal or hepatic blood flow: Hemorrhage, heart failure, cardiogenic shock
◦ Decreased renal function
◦ Decreased metabolism: Another drug inhibits its biotransformation, hepatic insufficiency
What situations will decrease a drugs half life?
◦ Increased hepatic blood flow
◦ Decreased protein binding - if drug is bound to proteins its not being metabolized. So decreased binding = more rapid elimination.
◦ Increased metabolism
• anything changing volume of distribution
What is first order elimination?
First order elimination: A constant fraction is eliminated per unit time. 50% of drug per hour. The half-life (T½) of a drug will be constant regardless of drug concentration
- volume cleared per unit of time by an organ is independent of PDC.
• The same volume of blood will be irreversibly cleared of drug by an organ regardless of how much drug is in the blood
This is that there is an constant
What happens if elimination mechanism becomes saturated?
If elimination mechanisms become saturated, elimination
becomes zero-order
What is zero order of elimination?
Less common
• Occurs only if so much drug is present in the blood that the organ of clearance becomes
saturated
• There is limited amount of enzyme and too much of the drug
• The rate of elimination of a drug from the plasma is constant regardless of the plasma
concentration of the drug
• The half-live is not meaningful. It is not constant and varies with the amount of the drug
concentration
What is an example of first order elimination? Why is half life important in these scenarios?
Assume a dog has ingested several aspirin to the point that the plasma drug concentration has surpassed the therapeutic range of 100 to 500 mg/mL and has achieved the toxic concentration of 2000 mg/mL. The half-life of aspirin in the dog is about 9 hours
First order: First-order elimination results in a concentration of 1000 mg/mL by 9 hours and 500 mg/mL at 18 hours. By 18 hours, the drug is back into the therapeutic range and by 36 hours, it approximates the low therapeutic range.
1st order -> half life is important because it is constant. Not so much in zero order.
What is an example of zero order elimination?
Assume a dog has ingested several aspirin to the point that the plasma drug concentration has surpassed the therapeutic range of 100 to 500 mg/mL and has achieved the toxic concentration of 2000 mg/mL. The half-life of aspirin in the dog is about 9 hours
For zero-order elimination a constant amount is eliminated per unit time. For example, if 100 mg/mL of aspirin is eliminated every 9 hours. By the time 36 hours has passed, concentrations will have declined to only 1600 mg/ml
In zero order, how does plasma concentration effect rate of elimination?
Zero order Rate of elimination will always be constant regardless of the plasma concentration/ dose.
Whether you have 1200 mg or 30,000 mg it will always decrease by a certain amount. Unlike 1st order which will decrease by 50% concentration each half-life.


