Volume of Distribution Concepts

Describe bioavailability:

the fraction of an administered substance that reaches the body’s systemic circulation; low bioavailability will have higher patient variability and vice versa

What does a bioavailability value (F) of 0.9 in contrast to a value of 0.2 say?

F implies how much of the drug remains; a value of 0.9 means that only 10% of the drug was metabolized (higher in value) as opposed to 80% for a value of 0.2

What does the parameter “S” represent?

salt factor, the fraction of dosage that is the active drug; calculated as the MW of the drug DIVIDED by the MW of the drug salt

How would you calculate an altered dose?

F₁ x S₁ x dose₁ = F₂ x S₂ x dose₂

What is the parameter “R_a” represent?

average rate that drug needs to reach systemic circulation; calculated as amount absorbed (Dose x F x S) divided by dosing interval (tau)

What percentage of the human body is water?

60%

From the total body water, what percent is intracellular fluid?

40%

From the total body water, what percent is extracellular fluid?

20%

From extracellular fluid, how much of it is interstitial fluid?

about ¾ (75%)

From extracellular fluid, how much of it is plasma?

about ¼ (25%)

What is the threshold for molecular size that molecules are able to travel into the interstitial space?

< 5000 Da

Define apparent volume of distribution:

• completely theoretical

• relates drug concentration in the body to drug concentration in blood plasma

• calculated as Cp = Dose/Vd

Define and name sequestration sites:

storage depot where drugs accumulate and are unavailable for therapeutic effect/prepared for excretion

• fat tissues

• bone

• tissues involved in protein binding

What is a “loading dose” and how is it calculated?

the initial dose needed to get to a therapeutic concentration in blood; calculated as Cp x Vd / (F x S)

What is “incremental loading dose” and how is it calculated?

total loading dose that is divided into smaller doses administered over a short period; calculated as V_d x (C_{p desired} - C_{p current}) / (S x F); assumes no excretion

What does the parameter “V_d” represent?

volume of distribution

• provides a sense of how far drugs distribute into compartments

• V_d tends to be high for highly lipid-soluble molecules

• V_d tends to be low for plasma-binding molecules

• V_d tends to be high for tissue-binding molecules

Drug X is highly, highly lipid soluble. Will it distribute throughout the body water?

Yes; it will distribute before eventually becoming stuck

Will the volume of distribution be higher or lower than the total body water volume?

Yes; V_d is theoretical so once widespread distribution is achieved, the apparent volume will appear larger than the actual physical volume