Expansion
The theoretical volume needed to contain the dose at the measured plasma concentration
Expansion
Volume of distribution = amount of drug in the body / plasma concentration
It is an apparent volume, not a real one, and may vastly exceed total body water.
| Drug | Approximate volume | Implication |
|---|---|---|
| Heparin, warfarin | 5 to 8 litres | Confined to plasma; highly protein bound |
| Aminoglycosides | 15 to 20 litres | Extracellular fluid |
| Digoxin | 500 litres | Extensive tissue binding |
| Amiodarone | over 5000 litres | Enormous tissue reservoir |
Determinants: lipid solubility, plasma protein binding (which reduces it) and tissue binding (which increases it).
Two practical uses:
- Loading dose = volume of distribution x target concentration. A drug with a large volume needs a large loading dose to fill the tissue compartment, which is why digoxin and amiodarone are loaded
- Dialysability: only drugs with a small volume can be removed by haemodialysis, because dialysis clears plasma. This is why lithium, salicylate and methanol are dialysable while digoxin and tricyclics are not
Volume of distribution also rises in oedema, pregnancy and sepsis, and falls in dehydration, requiring dose adjustment for water-soluble drugs.