Pharmacokinetics - distribution part 2 Flashcards
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
What is the equation to determine the elimination rate?
Indicate units.
Elimination rate (mg/h) = CL (L/hr) * Cp (mg/L)
Elimination rate varies directly with what?
Cp
Clearance is not directly related to ___, what is it related to?
CP
Instead, related to each individual person.
CL is a constant for each patient
When the plasma drug concentration is maintained at the therapeutic concentration, this meas the drug is?
bioavailable
Bioavailability is what?
The fraction of unchanged drug found in the systemic circulation
For a drug given by IV, bioavailability is what?
1
For an oral dosage form, what is bioavailability a function of?
Bioavailability (F) = fg * fh
Fg - fraction of drug asborbed
fh - fraction of the drug left after first pass metabolism
What is the AUC equation for bioavailability?
Bioavailability = AUCoral/AUCiv
Refer to slide 18 with the AUC curves.
What is the difference between Tablet A and Tablet B?
Between A, B and C, which has the lowest bioavailability?
A has faster/better absorbtion than does B.
C has the lowest bioavailability.
