Pharmacokinetics - distribution part 2

Question 1

What is the use of the Vd value?

Answer 1

For determination of the loading dose to give to a patient to reach a desired Cp.

Question 2

What is the equation to determine loading dose?

Answer 2

Loading dose = target Cp * Vd

Question 3

Vd is a parameter of the ______.

Answer 3

drug

Question 4

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

Answer 4

volume
hypothetical, fluid, distributes
virtual pool, observed
observed

Question 5

When is Vd determined?

Answer 5

During the phase 1 clinical trials.

Question 6

Describe the body fluid Rule of 60:40:20.

Answer 6

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)

Question 7

Describe a pattern 1 drug.

What is its vd?

Answer 7

Pattern one drugs have a high MW, are highly charged, and remain in the blood vessels after injection
Vd = 0.04 L/kg

Question 8

Describe a pattern 2 drug.

What is its vd?

Answer 8

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

Question 9

Describe a pattern 3 drug.

What is its vd?

Answer 9

Drug with a specific affinity towards organ- or tissue-specific molecules
Vd > 0.6L/kg

Question 10

Describe a pattern 4 drug.

What is its vd?

Answer 10

Most drugs show this pattern of distribution. They are found in the blood and in different tissues.
Vd > 0.6 L/kg

Question 11

A drug with a Cp that doesn’t change is consistent with what pattern of distribution?

Answer 11

Pattern 1, the drug stays in the blood.

Question 12

A drug with a Cp that rapidly drops is consistent with what pattern of distribution?

Answer 12

Pattern 2, the drug follows the distribution of water.

Question 13

A drug with a Cp that drops slightly or increases slightly is consistent with what pattern of distribution?

Answer 13

Patterns 3 and 4: the drug distributes throughout the total body fluid and is retained in some tissues/organs,

Question 14

What are factors that increase the drug plasma concentration?

Answer 14

Administration and distribution

Question 15

What are the factors that decrease the desired plasma drug concentration?

Answer 15

Elimination
- sweat
- urine
- feces
- shed skin
Metabolism

Question 16

What are the factors that can affect maintenance of a drug at the therapeutic concentration?

Answer 16

Add:
- administration
- distribution
Remove:
- elimination
- metabolism

Question 17

Drug elimination:

• ________ drug elimination
• _________ of unchanged drug in urine, sweat, expired air, feces
• _________ (drug ________): drugs are metabolized into a different compound

Answer 17

irreversible
excretion
biotransformation (Drug metabolism)

Question 18

What are the two factors of drug elimination?

Answer 18

Excretion

Metabolism/biotransformation

Question 19

Elimination is an _________ process.

Answer 19

irreversible

Question 20

What is clearance?

What are its units?

Answer 20

Clearance (CL) is defined as the volume of blood cleared of drug per unit time.
Reported in L/hr

Question 21

How is clearance measured?

Answer 21

By measuring plasma drug concentration at different intervals, following a single dose of medicine.

Question 22

What is the equation for clearance?

Indicate the units.

Answer 22

Clearance (L/hr) = Dose (mg) / AUC (mg*hr/L)

Question 23

For the AUC, what are the axes of the graph?

Answer 23

Y - Cp (mg/L)
x - time (hr)
AUC = xy
AUC = mghr/L

Question 24

What is the typical shape of the CP/time graph for an orally administered drug?

Answer 24

Cp builds up then drops down.

very left skewed distribution

Question 25

What is the equation to determine the elimination rate?

Indicate units.

Answer 25

Elimination rate (mg/h) = CL (L/hr) * Cp (mg/L)

Question 26

Elimination rate varies directly with what?

Answer 26

Cp

Question 27

Clearance is not directly related to ___, what is it related to?

Answer 27

CP
Instead, related to each individual person.
CL is a constant for each patient

Question 28

When the plasma drug concentration is maintained at the therapeutic concentration, this meas the drug is?

Answer 28

bioavailable

Question 29

Bioavailability is what?

Answer 29

The fraction of unchanged drug found in the systemic circulation

Question 30

For a drug given by IV, bioavailability is what?

Answer 30

1

Question 31

For an oral dosage form, what is bioavailability a function of?

Answer 31

Bioavailability (F) = fg * fh
Fg - fraction of drug asborbed
fh - fraction of the drug left after first pass metabolism

Question 32

What is the AUC equation for bioavailability?

Answer 32

Bioavailability = AUCoral/AUCiv

Question 33

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?

Answer 33

A has faster/better absorbtion than does B.

C has the lowest bioavailability.