Hepatic and Biliary Clearance Flashcards
Total clearance value calculated based on the plasma concentration-time data is considered the…
plasma clearance (CL)
Blood clearance (CLblood) can be calculated based on the CL and plasma-to-blood conc. ratio (C/Cblood)
CLblood=CL*(C/Cblood)
How to calculate fraction unbound in blood (fu,b)
fu,b = fu * (C/Cblood)
Unbound clearance is always ________ than the total clearance because ___________.
greater; only unbound drug can be eliminated
Hepatic clearance (CLh) can be defined as…
The volume of plasma (or blood for CLb,h) being cleared of drug per unit time during passage through the liver.
When used in the calculation of excretion ratio (ER), CLh MUST be converted to CLb,h first
CLb,h = CL x (1-fe) x (C/Cblood)
What is the ER?
ER -(extraction ratio) - I the fraction of blood being cleared during each pass through the liver
CL b,h
hepatic (blood) clearance
What cannot affect F?
Renal excretion cannot affect F
Ff
fraction of dose that enters the gut wall
Fg
fracton of dose in the gut wall that escapes elimination in the intestine
Fh
fraction of dose in the portal system that escapes elimination in the liver
If a drug is mainly eliminated in the liver and has a high ER value, its oral bioavailability should be-…
low
What is CLint
CLint is the intrinsic clearance which represents the ability of the liver to remove the drug from blood when there is no restriction on blood flow to the liver
The maximum possible value of CLb,h of any given drug is ___________ whereas here is ________ for the VLint value.
liver blood flow rate; no limit
The maximum possible value of hepatic clearance is the _______
hepatic blood flow rate
The maximum possible value of intrinsic clearance is_________
infinity
High ER
ER > 0.7
Low ER
ER < 0.3
intermediate ER
ER = 0.3-0.7
A decrease in hepatic blood flow will decrease __________ of a high ER drug
hepatic clearance
Decrease in metabolizing enzyme activity will decrease ___________ of a high ER drug.
intrinsic clearance
Decrease in hepatic blood flow will decrease _________ of a low ER drug.
neither hepatic nor intrinsic clearance
Decrease in metabolizing enzyme activity will decrease ________ of a low ER drug.
both hepatic and intrinsic clearance
Change in plasma protein binding will affect the hepatic clearance of _________ drugs
Low ER
Change in plasma protein binding will affect the intrinsic clearance of _________ drugs
both low and high ER
If a drug is 100% eliminated in the liver and has ER value of 0.88, its CL approximates ______
Qh
If a drug is 100% eliminated in the liver and has ER value of 0.28, its CL approximates _______
fu*CL’int
T/F - Does Css has an impact on fu
F - no impact of fu on Css
T/F - Cu,ss has direct relationship between Cu,ss and fu
True
For a high ER drug that is mainly eliminated in the liver, its total clearance approximates ________
hepatic blood flow rate
For a low ER drug that is mainly eliminated in the liver, its total clearance approximates _________
intrinsic clearance (or the product of fraction unbound in blood and unbound intrinsic clearance)
If a drug is mainly eliminated in the liver and has a volume of distribution valued of ~100L and a ER value greater than 0.7, its total clearance approximates _____ and its elimination half-life approximates.
CL~Qh; t1/2 = 0/693 x VT x fu/fuT/Qh
If a drug is mainly eliinated in the liver and has a vol of distribution value of ~100L and a ER value of ~0.25, its total clearance approximates __________ and its unbound conc. at steady state approximates ___________.
CL~fuxCL’int; Cu,ss = fuxRo/fuxCL’int = R0/CL’int
Biliary clearance is a proportionality constant relating _______ to ________.
excretion rate of unchanged drug in the bile; the plasma drug concentration
Drugs and metabolites that have MW of _________ and are ________ and prone to biliary secretion
> 500 Da; polar
Biliary excretion of a drug can be affected changes in ___________
active transporter activity
