Volume of Distribution

Mary Ramsaroop
 Remembering:
• -Concentration =Mass/Volume
• Ideal situation mass of drug will distribute in INTRAVASCULAR and
INTRAVASCULAR fluids evenly but not ideal.

• Volume of Distribution: is an apparent Volume of distribution and takes into

account the attributes of the drug in the person 
and so, tells where the drug likes to be in
relation to TBW
• Drugs that like Plasma: distributes in a small volume so, ~9L
• Drugs that like extravascular compartments: distributes in a larger volume so,
~ 40L
 Deriving Vd formula from
• - helps us to figure out how

• much of total drug to give to reach desired plasma concentration

• So Vd can be written as
•

• `
 how do we solve for vd…what goes in it?
• Drug:
• Size (MW)-
• Plasma protein binding - vs Extravascular Proteins –

• Lipophillic (Binds fat and not proteins) –

• Hydrophillic (really charged, ionized)-
• Unhealthy person-Protein deficient (most abundant is albumin, that a lot of drugs bind to)

• Increase Capillary permeability- Large drugs that couldn’t get out into the extravascular
circulation before can now
 Question: A drug with a large volume of distribution which has been taken in
• - overdose can be readily removed by dialysis. (Remember: dialysis only
removes free drug from the plasma.)

• Acidic molecules have a higher affinity for albumin molecules at lower lipophilicity than neutral or
basic molecules. Therefore, acidic drugs are more likely to bind albumin and remain in the plasma
leading to lower Vd
• Basic molecules will leave the systemic circulation leading to higher Vd
• Lipophilic molecules are more likely to pass through lipid bilayers and therefore more likely to leave
the bloodstream and distribute to areas with high lipid density (adipose) and therefore have
a higher Vd.
• Hydrophilic molecules are less likely to pass through lipid bilayers and therefore more likely to
remain in the bloodstream and therefore have a lower Vd.
 Question 1: a 60KG person has bacterial pneumonia and was given erythromycin iv. The minimum antibiotic concentration that will inhibit bacterial growth is 20mg/L. VOLUME OF DISTRIBUTION 0.70 L/KG . CALCULATE THE DOSE.

• -
 Question 2: a 60KG person has bacterial pneumonia and was given erythromycin ORALLY. The
minimum antibiotic concentration that will inhibit bacterial growth is 20mg/L. VOLUME OF
DISTRIBUTION 0.70L/KG. ORAL BIOAVAILABILITY IS 50%. CALCULATE THE DOSE.
• -
 Calculate the volume of distribution for:
1) JK is a patient who weighs 60 kg. She is given a 1000 microgram dose of Drug A. Drug A
distributes extensively into tissues, so that only a fraction of the original dose remains within the
plasma. On measuring the plasma concentration, we get a value of 2 micrograms per liter.
2) The same patient is given 350 milligrams of Drug B, which distributes throughout extracellular
fluid, but not readily into tissues. On measuring a peak level, we may get a value of 20 milligrams per
liter.
-
 2)Dose = Vd * desired concentration. What is the dose of gentamicin
required to obtain a peak level of 20 mg/L in a 60 kg patient? (The Vd for
gentamicin is 0.25 L/kg.)
• -