Drug Elimination Flashcards
Pharmacokinetic parameters of elimination for a specific drug describe the ____ and ______ of elimination
rate, extent
How is rate measured?
Half life (t1/2) or clearance
How is extent measured?
not measured, all of drug dose will ultimately be eliminated from the body
Clinical relevance of the steady state equation
How does blood flow to the liver effects hepatic clearance?
Low extraction drugs - clearance is not significantly influenced
High extraction drugs - changes have a major influence on clearance
What affects intrinsic hepatic metabolic activity?
subject to coadministration of inducers and inhibitors
3 factors that hepatic clearance varies with
- blood flow to liver
- intrinsic metabolic activity (inducers/inhibitors)
- Protein-drug binding (only free drugs metabolized)
What is used to monitor kidney function?
Serum creatinine (SCr), Creatinine Clearance (CrCl)
In first order kinetics what is the rate of elimination proportional to?
Rate is proportional to a rate constant X the Cp raised to the first power
Most clinically utilized drugs are eliminated by _____ order kinetics when given in therapeutic doses
first (99%)
Hepatic metabolism and renal excretion are ____ order processes
First
Describe first order kinetics
constant percent of drug eliminated per time, rate of drug eliminated is proportional to Cp and constantly changing
A drug eliminated by 1st order kinetics will generate straight line with a slope of ______, and the y intercept is ____
slope is Ke - the elimination rate constant
y intercept is Cp0 plasma concentration at time 0
What is half life and how is it determined?
Time required to eliminate half of the drug, used to describe rates of elimination
t1/2 = 0.693/ke
Half life is _______ proportional to clearance, and ________ proportional to Vd
inversely, directly
increase clearance = decrease half life
increase Vd = increase half life (and vice versa)
Half life is ______ of the total amount of drug present
independent
What determines the degree of fluctuation in plasma levels between doses?
The number of half lives in the dosing interval, mor half lives = more fluctuation
As a rule of thumb estimate, how long does it take for a drug to reach steady state when administered continuously?
4-5 half lives
As a rule of thumb estimate how long does it take a drug to be eliminated after the last dose?
4-5 half lives
What is zero order kinetics most often due to?
saturation of hepatic metabolism, especially in phase II conjugations
Describe zero order kinetics
The amount of drug eliminated per time is constant and independent of the plasma concentration, seen with very few drugs at therapeutic doses and many drugs at toxic doses
The amount of fluctuation in Cp tolerated for any dug is related to its __________ __________
Therapeutic Window
How can you slow absorption of a drug and blunt the fluctuations in Cp?
extended release preps
Calculate the degree of fluctuation for a drug if t1/2 = 24 hrs and the drug is dosed every 3 days
(T/t1/2) Dosing time/half life = 72hrs/24hrs = 3 –> 2^3 = 8
