Exam 3: Basic of Pharmacokinetics II Flashcards
PK
What the body does to the drug
PD
What the drug does to the body
Volume of Distribution
Theoretical volume that the drug homogeneously distributes into
Vd formula
Amount of drug (mg) / Drug plasma conc. (mg/L)
Vd units is L
Drug in the blood is distributed to various organs
- Distribution to heart, liver, kidneys, and brain is rapid
- Distribution to muscle and skin is slower
- Distribution to bone and fat is even slower
Distribution models: One-compartment
- Single, uniform compartment
- Assumes instantaneous distribution
- And immediate start to elimination
Distribution models: Two-compartment
Two compartments
• Central compartment
• Peripheral compartment
Assumes instantaneous distribution to central compartment
• And immediate start to elimination
Central compartment
-High perfused tissues like: • Blood • Liver • Kidney • Heart • Lungs
Peripheral compartment
Poorly perfused tissues
• Fat, muscle, CSF
Which parts of ADME constitute elimination?
- Metabolism
* Excretion
In which organs does metabolism primarily take place?
- Liver
- Lungs
- Small intestine, skin
In which organs does excretion primarily take place?
- Kidneys
* Lung
Clearance
Volume of blood from which drug is removed per unit time
Expressed in volume/time (L/hr)
- Its additive in that you can add the volume of blood from which drug is removed in each organ
Hepatic clearance
Liver metabolism
Biliary excretion
excretion via feces
Renal clearance
excretion via urine
high drug clearance
60-90 L/hr
Medium drug clearance
30-60 L/hr
low drug clearance
< 30 L/hr
How many L of blood are in the human body?
5 L
The heart pumps the entire volume in
1 minute (approximately)
Rate of elimination (Re)
how much drug is eliminated per unit time
- Dependent on drug conc.
Rate of elimination formula
Drug plasma conc. * Clearance
Units are mg/hr
The higher the conc. of drug,
the faster it is cleared
Most drugs are cleared by
First order elimination
What does not change in rate of elimination problems?
Vd and clearance
More substrate ->
more product
More drug ->
more elimination
As the plasma conc. of drug increases,
the rate of elimination increases
The rate of drug removal is
directly proportional to the concentration of drug
As Half life decrease,
the clearance goes up
Longer half life means
lower clearance