Clinical Pharmacokinetics II Flashcards
Define hepatic extraction ratio:
The fraction of a drug extracted by the liver in first pass metabolism
Relationship of bioavailability and hep. extr. ratio
Bioavailability = 1-Extraction Ratio
Bioavailability of an IV drug
1
Changing hepatic activity will have a low effect on a drug with a _______ Eh
low
Changing hepatic activity will have a high effect on a drug with a _______ Eh
High
What does it mean to say two drugs are bioequivalent
The extent and rate of absorption of the drug are so similar that there is likely no clinically important difference between their effects
If 100% of drug is absorbed through gut, how to calculate bioequiv?
F=1-Eh
Mathematical requirements for bioequivalence
90% confidence interval of the AUC ratio between 0.8 and 1.25
Only unbound drug is ______
active
Other than the target tissue, where else may the drug distribute
Fat
Other tissues
plasma proteins
What drugs tend to be excluded by cell membranes
Very polar drug molecules
What drugs tend to be confined to circulation
Very large ones
What is Vd
The constant relating the amount of drug in the body to the plasma drug concentration
Equation for Vd
(total amount of drug in the body)/Plasma drug concentration
Give an example of a situation with a very low apparent volume distribution
High amounts of a substance are protein bound in the plasma
Give an example of a situation with a very high apparent volume distribution
drugs absorbed and retained in the fat cells, leaving very little in the plasma
Influence of dose on Vd? Concentration?
None
Vd is a constant
What does steady state mean?
The condition in which the average total amount of drug in the body remains stable over time of dosing
(input=elimination)
What is a maintenance dose rate
Mass/Time of drug input to maintain the drug concentration in steady state
What do you provide to give an initial appropriate drug level before maintenance doses?
Loading Doses
Loading dose equation
(Vd)(target plasma conc)
What is metabolism?
The irreversible transformation of parent compounds into daughter compounds
Metabolism diminishes drug activity in what two ways
Inactivation and Elimination
How are most drugs excreted?
Via the kidney
Define Clearance
- The efficiency that the drug (vol) is irreversibly eliminated from the volume of distribution
- Final value should be vol/time
Define Elimination Rate
The amount of the drug (mass) that is irreversibly eliminated form the dose per unit time
Elimination Rate Equation
ER = (Clearance)*(Plasma Concentration)
Define Elimination Rate Constant
The fraction of the drug volume that is irreversibly eliminated from the volume of distribution per unit time
Elimination Rate Constant Equation
K = Clearance/Volume of Distribution
ex. 20% of drug/hour
Increasing the plasma concentration of a drug will ______ its ER
Increase it
ER=CL(Cp)
At steady state, Maintenance dose rate =
Elimination Rate
Maintenance dose rate equation =
(Clearance) (Steady state drug Conc)
Equation for organ clearance
CL= Organ Extraction Ration (Organ Blood Flow)
