Lecture 32 Flashcards
What are three important pharmacokinetic parameters?
- volume of distribution
- clearance
- bioavailability
What is volume of distribution and how is it measured?
Relates the amount of drug in the body to the concentration of drug in the plasma
Vd = amount of drug in body over plasma drug concentration
What does Vd (volume of distribution) represent?
Vd is the volume that would be required to contain all of the drug in the body at the same concentration as it is in the blood.
What does a low Vd mean?
high in the vascular and low in the extravascular
what does a high Vd mean?
low in the vascular and high in the extravascular
What is the main use of the volume of distribution?
The main use of the volume of distribution is to determine the loading dose to quickly achieve a target plasma concentration.
How to determine Vd?
Vd = dose over C0
C0 = concentration at time zero
What are the two phases of a Vd graph?
The rapid fall phase = distribution
The slower phase = elimination
What is clearance defined as?
defined as the volume of blood cleared of drug per unit time
clearance predicts the rate of elimination of a drug in relation to the drug concentration
What are the two major sites of drug elimination
kidneys and the liver
What is first-order elimination?
For a drug eliminated with first-order kinetics, CL is a constant, ie, the ratio of the rate of elimination to the plasma concentration is the same regardless of plasma concentration
why do most drugs follow first- order elimination?
This occurs because the physiological mechanisms of drug elimination (enzymes and transporters) are not
saturated
the plasma concentration is below the Km
What is half-life?
Half-life determines the rate at which blood concentration rises during a constant infusion and falls after infusion is stopped
at steady state
During a constant IV infusion of a drug (half-life)
50% of Css is reached after 1 half-life
• 75% after 2 half-lives
• 87.5% after 3 half-lives
• 93.75% after 4 half-lives
vise versa for elimination
how to change the Css?
2x the infusion rate
What factors impact half-life
obesity = increases
pathologic fluid = increases
aging = increased
cardiac, liver, renal failure = increase
CYP induction = decreases
CYP inhibition = increases
Why do some drugs show saturation kinetics?
Drug metabolism and tubular secretion are
saturable processes.
When drug concentration exceeds Km, nonlinear
kinetics is observed
Which drugs show saturation kinetics?
aspirin at high doses
ethanol
phenytoin
properties of saturation kinetics
elimination is zero order
a constant amount of drug is eliminated per unit time
The rate of elimination is maximal and independent of drug concentration
What does a saturation kinetics graph look like?
linear
What is not applicable with saturation kinetics?
the concept of “4 half-lives to steady state” is NOT applicable for drugs with nonlinear elimination kinetics
