Pharmacokinetics

Question 1

What are the likely compartments of distribution according to volume of distribution ranges?

Answer 1

Vd represents the degree to which a drug is distributed in body tissue rather than the plasma.

Vd <4L : confined to plasma
Vd 4-7L : blood (plasma + RBCs)
Vd 12-20L : extracellular space
Vd >42L (total water volume) : highly distributed into tissue (especially, but not always, indicating fatty tissue)

Question 2

What could increase or decrease volume of distribution?

Answer 2

Patient factors
*Accumulation of fat is important for lipid soluble drugs, accumulation of fluid for water soluble.
Smaller Vd: dehydration, females (less body water), older age (body water decreases, muscle mass i.e. tissue binding decreases)
Larger Vd: pregnancy (increased body water & fat, amniotic fluid), oedema/ascites/effusions (water soluble drugs) i.e. kidney failure & liver failure (also decreased proteins for binding)

Drug factors
Smaller Vd: larger the molecule, highly ionised/highly water soluble (more limited to extracellular space), plasma protein binding
Larger Vd: highly lipid-soluble, increased tissue binding

Question 3

Vd = ?

Answer 3

Amount of drug in the body (dose)
divided by
plasma concentration

Determined in conditions under which the drug distribution between the plasma and the tissues is at equilibrium

Question 4

Explain renal clearance (Clx) of a drug in mL/min.

Answer 4

The volume of plasma that the kidneys completely clear of that drug (the volume cleaned) per unit of time.

Clx (mL/min) = urine concentration mg/mL x
[urine flow rate mL/min / plasma concentration mg/mL]