Lecture 8 2/13/24 Flashcards
When does plasma protein binding matter?
-quick plasma-tissue equilibrium time
-narrow therapeutic window
Which two characteristics of pharmacokinetics are dependent on physiology?
-Vd
-Cl
What drives Kel?
-Vd
-Cl
What is the equation for half-life?
HL = 0.693/K
What is the equation for K?
Cl/Vd
What is the main characteristic of hybrid parameters?
depend on other parameters
What is a half-life?
time that it takes for the drug concentration in plasma to decline by 50%
In which type of process is half-life a constant value?
first order
Why does high clearance not always lead to a short half-life?
if a drug distributes extensively in the tissues, there will not be enough drug in the plasma to clear at the high clearance rate
What is the limiting factor of high extraction?
blood flow/speed at which a drug is brought to the liver
What is the limiting factor of low extraction?
liver capacity for elimination of the drug
What are the potential characteristics of long-acting drugs?
-high plasma protein binding
-high volume of distribution
-slow release from administration site
What factors play into selecting a dose interval?
-half-life
-therapeutic index
-compliance
When is a drug considered to be majority eliminated from the body?
after 4-6 half-lives
What is a steady state?
point where the rate of drug coming in is the same as the rate of drug being eliminated
What determines the time it takes to reach steady state?
rate of drug elimination
What effect does half-life have on steady state?
-a drug with a shorter half-life will reach steady state sooner
-a drug with a longer half life will reacher steady state later
Why is steady state irrelevant for drugs with very short half-life values?
the drug does not accumulate with repeat dosing
What is a loading dose?
-increased initial dose that helps a drug get into the therapeutic range quickly
-followed up by maintenance dose(s)
Which factors impact half-life?
volume of distribution
-clearance
Which factors impact systemic exposure?
-clearance
-bioavailability
What is clearance in first order systems?
proportionality constant between the rate of elimination and the concentration of drug in the system
What is the calculation for intravenous dose?
dose = Cl x AUC
What is the calculation for extravascular dose?
dose = (Cl/F) x AUC
What is the equation for infusion rate?
Inf. rate = Conc. steady state x Cl
What is the equation for loading dose?
LD = Vd x Conc. steady state
How can a new dose be calculated from an old dose when half-life is long?
new dose = old dose x (Conc. target min./Conc. measured min.)
What is the theoretical equation for clearance?
Cl = Kel x Vd
What is the theoretical equation for volume of distribution?
Vd = dose/C0
