Drug Clearance Flashcards
Drug clearance is measured in what units?
volume/time (mL/min)
What is the formula(s) for Cl?
Cl = elimination rate (mg/min) / plasma conc (mg/mL)
Cl = Vd x K
Cl = Q x ER
In the formula Cl = Q x ER,
What does Q and ER stand for?
Q = blood flow ER = extraction ratio
What does Clr stand for?
renal clearance
What are the formula(s) for Clr?
Clr = Qu x Cu / Cp
Clr = filtration rate + secretion rate - reabsorption rate / Cp
What is the clearance ratio?
Cl drug / Cl inulin
If clearance ratio < 1 = ?
partially reabsorbed
If clearance ratio = 1 ??
filtered only
If clearance ratio > 1 = ??
actively secreted
What is happening if the graph is curved?
You know that both secretion and filtration are happening
What kind of graph would tell you that only filtration is happening?
straight line
What is the formula for free amount of drug (Cpfree)
Cpfree = (1-alpha) Cp
free amount = free fraction x total amount
What does (1-alpha) mean?
free amount
What does fe stand for?
fraction of drug excreted
What does R stand for?
infusion rate
What does Css mean?
steady state [drug]
What are the formulas for clearance after IV infusion?
Cl = R/Css Cl = k x Vd
What is hepatic clearance affected by?
- blood flow
- intrinsic Cl
- protein binding
What does Clh mean?
hepatic clearance
What is the formula for hepatic clearance?
Clh = [Q(Ca-Cv)]/Ca = Q x ER
What does Ca mean?
arterial concentration
What does Cv mean?
venous concentration
What does Clint stand for?
intrinsic clearance
For some drugs that are ____ extracted, the extraction ratio is greater than 0.7
highly
What does highly extracted mean?
That the liver removes the drug almost as fast as its delivered to it.
Highly extracted drugs:
An increase in blood flow will _____ the organ (hepatic) clearance rate.
increase
Highly extracted drugs:
Are known as _____ ____ limited or ____ ____ sensitive
(same answer for both blanks)
blood flow
Highly extracted drugs:
For drugs that affect ____ ______ it also decreases organ blood flow and as such will decrease its own clearance rate
cardiac output
Drugs that are ____ extracted by the organ have an extraction ratio (ER) of about 0.1 to 0.4
poorly
Poorly extracted drugs:
Does blood flow affect clearance rate?
No - a change in organ blood flow doesn’t really affect the clearance rate.
Poorly extracted drugs:
Drugs that are poorly extracted are known as ______ limited
enzyme
Poorly extracted drugs:
If you induce the enzymes that are responsible for metabolizing the drugs, how will hepatic clearance be affected?
it will go up significantly.
Poorly extracted drugs:
If you induce the enzymes that are responsible for metabolizing the drugs, how will biliary clearance be affected?
clearance will also go up for drugs eliminated via the biliary excretion
Poorly extracted drugs:
Why do poorly extracted drugs have variable half-lives and clearance rates?
- because patients have much different timers of hepatic enzymes
- thus, much different extraction ratios occur for the same drug in different people which results in much different clearance rates
What is Intrinsic Clearance (Clint) used to describe?
- the ability of the liver to remove the drug in the absence of any flow limitation
- this reflects the inherent activity of the mixed-function oxidases
What does it mean if Q > Clint?
blood flow is not the limiting factor
What does it mean if Clint > Q ?
you have tons of enzymes, they are not the limiting factor
Drug protein binding is not a factor in hepatic clearance for drugs that have ___ extraction ratios
high
Drugs that have low extraction ratios may be affected by plasma ____ _____ depending on the fraction of drug bound to proteins
protein binding
For drugs that have low extraction ratios and low binding to plasma proteins, _____ changes in protein binding would not produce any significant changes in hepatic clearance
small
Drugs with low extraction ratios and low binding to plasma proteins are ???
capacity-limited, binding insensitive drugs
Drugs with low extraction ratios are high binding to plasma proteins are ??
capacity-limited binding sensitive drugs
*because a small displacement in the protein binding of these drugs will cause a very large increase in the free drug concentration
