Drug Distribution and Vd - Pre Lecture Flashcards
What is drug distribution?
The post-absorption transfer of drug from one location in the body to another
What does measured drug concentration in plasma reflect?
The amount of drug in the body and how extensively the drug is distributed throughout the body
Why is 1COM model not adequate to analyze drug distribution?
Drug distribution is assumed instantaneous
What model is used to measure drug distribution?
Multi-compartment
What is apparent volume of distribution?
The lack of true volume because the peripheral tissue compartments are not easily sampled to know their true volume
What is distributional clearance?
The estimation of the rate of drug transfer between compartments
What is Vd?
The extent of drug distribution
What is the definition of apparent Vd?
The hypothetical volume that relates the amount of drug in the body to its plasma concentration measures at time
What is the equation of Vd?
Vd(t) = A(t)/Cp(t)
What is A(t)?
The amount of drug in the body at time after dose
What is Cp(t)?
Plasma concentration of drug at time t
What is Vd(t)?
The apparent volume of distribution with respect to the drug
concentration in the plasma at time = t
Describe the distribution of 1COM drug?
Drug distributes instantaneously in central compartment and doesn’t move to peripheral compartment
Vd = Vc (central compartment)
Describe the distribution of 2COM drug?
Movement from central compartment to peripheral compartments
What are the 3 Vd that measured plasma concentration-time curve?
Vc, Css, Vb
What are the characteristics of Vc?
- Volume of distribution in central compartment
- It ONLY relates the amount of drug in central compartment to its concentration in the central compartment.
- It represents the volume of distribution during early distribution-phase.
What are the characteristics of Vss?
- Volume of distribution at steady state
- At steady state, the net movement of drug between the central & peripheral compartments is 0.
- 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).
- 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
What is the most clinically relevant that is used to determine loading dose of a drug?
Vss
What is Vb?
- Volume distribution at pseudo-distribution equilibrium anytime during elimination phase
- 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.
- The volume of distribution at pseudo-distribution equilibrium (Vβ) relates the total amount of a drug present in the body during the elimination-phase.
How do you find Vb?
Vb = Cl/B
How is LD calculated?
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.
What inherent drug properties that influence Vd?
- Extremely high or low polarity or non-polarity
- Drug molecules size
- Extensive plasma or tissue protein binding of drugs
- role of drug transport system in transferring drug across biological membrane,
- disease states that cause changes in the body fluids volume
What is the Vd difference between pediatric and adult dosing?
As body composition changes with aging, drug distribution will also change that loading does between pediatrics and adults are different
What is the Ld difference between obese and non-obese?
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
