Tissue Distribution (3)

The illustration provides some examples of drugs with various apparent volumes of distribution. For comparison, a human (aldult) body has a total body volume of around 60 litres (details here). 

  • Warfarin: Has a high degree of plasma protein binding, resulting in a relatively low Vd.
  • Ethanol: Hydophilic compound (LogP -0.2) that distributes over the body water (~40 L).
  • Digoxin: Lipophilic drug (LogP 2.4) that distributes into fats and (cardiac) muscles (particularly the Na+/K+-ATPase transporter protein) and has a high Vd of 640 L.
  • Chloroquine: Highly lipophilic drug (LogP 4.6) that accumulates in body fat tissue. Known for its high Vd around 15.000.

See how distribution to different tissues will effect drug concentrations by clicking here and selecting the Vd and loading dose (module 4).

 

Now returning to the gentamicin example. What is the apparent volume of distribution of gentamincin (in L/kg) if a 160 mg intravenous injection of gentamicin in a 70 kg man produces a concentration of 7 µg/mL?

Answer:

Vd = Dose / Concentration = 160 mg / 7 mg/L = ~22.9 L. This distribution volume is observed in a 70 kg man, thus the apparent Vd of gentamicin = 22.9L / 70kg = ~0.33 L/kg

Unfortunately, this measured peak concentration is lower than the desired >8µg/mL. Therefore, what IV-dose would you give to achieve doses around 10.5 µg/ml?

Gentamicin Dose = Vd · Concentration = 22.9 L · 10.5 mg/L = 240 mg.

1

Warfarin has a volume of distribution of 8 L. If the plasma concentration is 1 mg/L, how much drug (in mg) is in the body?
(only provide the number, not the unit)

2

Warfarin has a volume of distribution of 8 L. If the plasma concentration is 1 mg/L, how much drug (in mg) is in the plasma, assuming a plasma volume of 3 litres? 

(only provide the number, not the unit)

3

Warfarin has a volume of distribution of 8 L. If the plasma concentration is 1 mg/L, how much drug (in mg) is in the tissues? (Still assume a plasma volume of 3 litres)

(only provide the number, not the unit)

4

Warfarin has a volume of distribution of 8 L. If the plasma concentration is 1 mg/L, what percentage of the drug in the body is in the tissues? (Still assume a plasma volume of 3 litres)

(only provide the number in 1 decimal, not the unit (e.g. 99.9))