Pharmacokinetics II (Herbert Ho, MD) Flashcards
What two parameters are used to define systemic exposure of a drug for comparison purposes?
AUC and Cmax
What method is used to compute the area of the ascending portion of the curve?
Linear Trapezoidal Method
What method is used to compute the area of the descending portion of the curve?
Logarithmic Trapezoidal Method
T/F: Cmax may change, but AUC may remain the same.
True
What are the two phases represented in a two compartmental model graph?
Distribution
Terminal
Does elimination occur during the distribution phase?
Yes
Does distribution occur during the elimination phase?
Yes
Describe the graph of a two compartmental model
Initially, there is rapid decline due to elimination from central compartment and distribution to peripheral compartment.
After time t, drug begins to flow back into central compartment and concentration in both compartments will decrease proportionally.
What is the formula for volume of distribution of the central compartment in a two compartment model?
V = A/(C1 + C2)
What is the central compartment in a two compartmental model?
Highly perfused organs like the blood, liver, ECF and kidneys
What is the peripheral compartment in a two compartment model?
Poorly perfused tissue such as muscle and adipose
What is the formula for volume of distribution of the peripheral compartment in a two compartment model?
V2 = V1 x k12/k21
What is the formula for steady state volume of distribution?
Vss = V1 (1 + k12/k21)
What is an indirect parameter used to estimate bioavailability?
AUC
What are the barriers that limit bioavailability of oral drugs into the body?
CYP450 3K5 (gut wall metabolism) CYP450 3K4 (hepatic metabolism)
What are the three bioavailability values you have to consider for an oral dose?
Fabsorption
FGI
Fhepatic
Multiplication and not addition!
T/F: F = AUCoral/AUCIV
False
This is only true if the doses are the same.
T/F: Relative bioavailability can be greater than 1.
True
What does multiple dose lead to?
Accumulation
How many half-lives are required to reach steady state?
4 - 7
What is the purpose of giving a loading dose?
To achieve therapeutic concentrations as soon as possible
Give the formula for loading dose
LD = Target dose x Vd/F
What are the assumptions behind the concept of a maintenance dose?
- Amount absorbed = amount eliminated
2. Dosing rate = elimination rate
Give the formula for dosing rate
Dosing rate = Clearance x Css
T/F: Css(ave) is the exact point where AUC is divided equally in half.
True
What is the formula for the new dosing rate?
New Rate = Old Rate x (Desired Css/Measured Css)
Is loading dose affected by clearance?
No
T/F: Dosing interval is commonly the same as half-life
True
What is the formula for maximum dosing interval?
MDI = ln[Cmtc/Cmec]/ke
What will longer dosing interval result in?
The concentration may rise above mtc or fall below med.
T/F: It is only in the initial stages of first-order kinetics that there is drug accumulation.
True
In zero order kinetics, there is accumulation all throughout.
T/F: In zero order kinetics, there is a constant rate of elimination over time.
True
What drugs become saturated at concentrations within the therapeutic range?
Phenytoin
Aspirin (ASA)
Carbamazepine
Ethanol
Where is there first-order kinetics at work?
If an enzyme is involved in the elimination of the drug
What is the formula for the rate of elimination in Michaelis-Menten kinetics?
Elimination = (Vmax x C)/(Km + C)
What is the relationship between ethanol and clearance? Ascorbic acid and clearance?
Increasing concentration of ethanol leads to decreasing clearance
Increasing concentration of ascorbic acid leads to increasing clearance
