Drug Distribution and Vd - Pre Lecture

Question 1

What is drug distribution?

Answer 1

The post-absorption transfer of drug from one location in the body to another

Question 2

What does measured drug concentration in plasma reflect?

Answer 2

The amount of drug in the body and how extensively the drug is distributed throughout the body

Question 3

Why is 1COM model not adequate to analyze drug distribution?

Answer 3

Drug distribution is assumed instantaneous

Question 4

What model is used to measure drug distribution?

Answer 4

Multi-compartment

Question 5

What is apparent volume of distribution?

Answer 5

The lack of true volume because the peripheral tissue compartments are not easily sampled to know their true volume

Question 6

What is distributional clearance?

Answer 6

The estimation of the rate of drug transfer between compartments

Question 7

What is Vd?

Answer 7

The extent of drug distribution

Question 8

What is the definition of apparent Vd?

Answer 8

The hypothetical volume that relates the amount of drug in the body to its plasma concentration measures at time

Question 9

What is the equation of Vd?

Answer 9

Vd(t) = A(t)/Cp(t)

Question 10

What is A(t)?

Answer 10

The amount of drug in the body at time after dose

Question 11

What is Cp(t)?

Answer 11

Plasma concentration of drug at time t

Question 12

What is Vd(t)?

Answer 12

The apparent volume of distribution with respect to the drug
concentration in the plasma at time = t

Question 13

Describe the distribution of 1COM drug?

Answer 13

Drug distributes instantaneously in central compartment and doesn’t move to peripheral compartment
Vd = Vc (central compartment)

Question 14

Describe the distribution of 2COM drug?

Answer 14

Movement from central compartment to peripheral compartments

Question 15

What are the 3 Vd that measured plasma concentration-time curve?

Answer 15

Vc, Css, Vb

Question 16

What are the characteristics of Vc?

Answer 16

1. Volume of distribution in central compartment
2. It ONLY relates the amount of drug in central compartment to its concentration in the central compartment.
3. It represents the volume of distribution during early distribution-phase.

Question 17

What are the characteristics of Vss?

Answer 17

1. Volume of distribution at steady state
2. At steady state, the net movement of drug between the central & peripheral compartments is 0.
3. The time at which steady state occurs is tss and the volume of distribution of the drug at tss is called volume of distribution at steady state (Vss).
4. Although it does not represent a real physiological volume, the volume of distribution at steady state (Vss) is used to assess the extent of distribution of a drug from the plasma into the tissues

Question 18

What is the most clinically relevant that is used to determine loading dose of a drug?

Answer 18

Vss

Question 19

What is Vb?

Answer 19

1. Volume distribution at pseudo-distribution equilibrium anytime during elimination phase
2. At the pseudo-distribution stage, the ratio of the amounts of a drug between central and peripheral compartments remains constant. The apparent volume of distribution of a drug during this phase is called Vβ.
3. The volume of distribution at pseudo-distribution equilibrium (Vβ) relates the total amount of a drug present in the body during the elimination-phase.

Question 20

How do you find Vb?

Answer 20

Vb = Cl/B

Question 21

How is LD calculated?

Answer 21

LD=Vss *TargetCp
Vss :volume of distribution at steady state
Target Cp is the plasma concentration of a drug that is targeted to be achieved after
its dose administration.

Question 22

What inherent drug properties that influence Vd?

Answer 22

1. Extremely high or low polarity or non-polarity
2. Drug molecules size
3. Extensive plasma or tissue protein binding of drugs
4. role of drug transport system in transferring drug across biological membrane,
5. disease states that cause changes in the body fluids volume

Question 23

What is the Vd difference between pediatric and adult dosing?

Answer 23

As body composition changes with aging, drug distribution will also change that loading does between pediatrics and adults are different

Question 24

What is the Ld difference between obese and non-obese?

Answer 24

The LD may be calculated based on different types of weights such as total body weight vs ideal bodyweight depending on the PK of specific drugs such as high polarity or non-polarity to prevent over or under dosing

Question 25

How does conditions affecting plasma protein concentration affect LD

Answer 25

The excess or deficiency of plasma proteins may affect the amount of drug that remains in the plasma and therefore Vd