Lecture 6 2/6/24 Flashcards
What is clearance?
-overall ability of the living organism to eliminate a drug
-most important pharmacokinetic parameter
What is the formal definition of clearance?
rate of drug elimination scaled by plasma concentration
What is the operational definition of clearance?
volume of plasma cleared by time unit
What impacts the amount of drug contained in the cleared volume?
the concentration/dose of the drug
What is the rate of elimination for first order pharmacokinetics?
rate of elimination = constant x concentration
How does clearance differ between first order and zero order?
-clearance is constant in first order
-clearance is not constant in zero order
What can a clinician control in order to impact clearance?
dosage regimen
-administration route
-dose
-frequency
What are the components of clearance?
-blood flow to the organ
-unbound drug fraction
-intrinsic clearing capacity of the organ
How does clearance relate to blood flow and organ extraction?
clearance = blood flow x organ extraction
How does clearance relate to dose and area under the curve?
clearance = dose/AUC
What is capacity dependent clearance?
clearance dependent on what the machinery within a clearance organ can do
What is capacity independent clearance?
clearance dependent on how quickly blood flow can bring the substance to the clearance organ
What are the dependent factors for high extraction?
blood flow to organ
What are the dependent factors for intermediate extraction?
-blood flow to organ
-intrinsic clearing capacity
-protein binding
What are the dependent factors for low extraction?
-intrinsic clearing capacity
-protein binding
What is the equation for extraction?
Ebody = body clearance/cardiac output
What can impact high extraction?
-variations in renal and liver blood flow
-anything else that alters blood flow
What can impact low extraction?
-enzymatic metabolism induction or inhibition
-altering capacity
-changes in protein binding
What is CL/F?
clearance for routes other than IV admin.
Which drug molecules are involved in equilibrium?
only those NOT bound to plasma proteins
Why is free fraction not the same as free concentration?
drugs released from plasma protein binding will quickly distribute into the rest of the body fluids
What is the reality of protein binding in low extraction?
-clearance increases in parallel to the increase in free fraction
-bound drug concentration decreases while free concentration barely changes
In which situation can free concentration increase with increased displacement?
high extraction drugs that are highly bound to plasma proteins, exhibit quick plasma-tissue equilibration time, and have a narrow therapeutic window
What truly happens if one drug displaces another?
-unbound fraction increases
-more free drug is available for distribution and elimination
-total drug concentration is lower
-free drug concentration returns to original value
What are the three things that can lead to a drug being long-acting?
-highly protein bound: creates storage pool
-high volume of distribution: gets drug into the tissues quickly so it is not in the plasma to be eliminated
-slow release from site of administration
