Pharmacokinetics - distribution part 2 Flashcards
(33 cards)
What is the use of the Vd value?
For determination of the loading dose to give to a patient to reach a desired Cp.
What is the equation to determine loading dose?
Loading dose = target Cp * Vd
Vd is a parameter of the ______.
drug
Apparent volume of distribution - Vd:
- Not a real ______
- a ________ volume of ______ into which the drug ________
- Volume of the _____ ______ of liquid required to account for the ________ drug concentration in the body
- ________ concentration might not be the desirable concentration
volume
hypothetical, fluid, distributes
virtual pool, observed
observed
When is Vd determined?
During the phase 1 clinical trials.
Describe the body fluid Rule of 60:40:20.
60% is body water that is easily accessible (0.6 L/kg)
- 40% is intracellular water (0.4)
- 20% is extracellular water (0.2)
- 4% is plasma (0.04)
- 16% is interstitial fluid (0.16)
Describe a pattern 1 drug.
What is its vd?
Pattern one drugs have a high MW, are highly charged, and remain in the blood vessels after injection
Vd = 0.04 L/kg
Describe a pattern 2 drug.
What is its vd?
Drugs that have a low MW and are able to follow the distribution of water molecules to enter and leave the cells and interstitial fluid.
0.04 < Vd = 0.6 L/kg
Describe a pattern 3 drug.
What is its vd?
Drug with a specific affinity towards organ- or tissue-specific molecules
Vd > 0.6L/kg
Describe a pattern 4 drug.
What is its vd?
Most drugs show this pattern of distribution. They are found in the blood and in different tissues.
Vd > 0.6 L/kg
A drug with a Cp that doesn’t change is consistent with what pattern of distribution?
Pattern 1, the drug stays in the blood.
A drug with a Cp that rapidly drops is consistent with what pattern of distribution?
Pattern 2, the drug follows the distribution of water.
A drug with a Cp that drops slightly or increases slightly is consistent with what pattern of distribution?
Patterns 3 and 4: the drug distributes throughout the total body fluid and is retained in some tissues/organs,
What are factors that increase the drug plasma concentration?
Administration and distribution
What are the factors that decrease the desired plasma drug concentration?
Elimination - sweat - urine - feces - shed skin Metabolism
What are the factors that can affect maintenance of a drug at the therapeutic concentration?
Add: - administration - distribution Remove: - elimination - metabolism
Drug elimination:
- ________ drug elimination
- _________ of unchanged drug in urine, sweat, expired air, feces
- _________ (drug ________): drugs are metabolized into a different compound
irreversible
excretion
biotransformation (Drug metabolism)
What are the two factors of drug elimination?
Excretion
Metabolism/biotransformation
Elimination is an _________ process.
irreversible
What is clearance?
What are its units?
Clearance (CL) is defined as the volume of blood cleared of drug per unit time.
Reported in L/hr
How is clearance measured?
By measuring plasma drug concentration at different intervals, following a single dose of medicine.
What is the equation for clearance?
Indicate the units.
Clearance (L/hr) = Dose (mg) / AUC (mg*hr/L)
For the AUC, what are the axes of the graph?
Y - Cp (mg/L)
x - time (hr)
AUC = xy
AUC = mghr/L
What is the typical shape of the CP/time graph for an orally administered drug?
Cp builds up then drops down.
very left skewed distribution
