Distribution (pharmacology)

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• Volume of distribution
  • $V_d=\frac{\text{amount of drug in the body}}{\text{plasma drug concentration}}$
  • Theoretical value, if the drug totally stays in bloodstream, how much plasma volume is needed?
    • Low Vd: If a drug has a low V_d (e.g., close to the plasma volume, ~3-5 L), it means the drug tends to stay within the bloodstream (plasma). The measured plasma concentration is relatively high compared to the total dose given.
    • High Vd: If a drug has a high V_d (e.g., hundreds of Liters, way more than normal plasma volume), it means the drug doesn’t stay in the plasma. It distributes extensively out of the bloodstream and into other tissues (like fat, muscle, organs). This leaves only a small fraction of the total drug in the plasma, resulting in a low measured plasma concentration relative to the total dose. To account for the entire dose at that low plasma concentration, the calculated “volume” needed becomes very large – hence, a high Vd.
  • Liver and kidney disease increase V_d (↓ protein binding, ↑ V_d).
  • Drugs may be distributed in more than one compartment.
  • Hemodialysis is most effective for drugs with a low V_d.

Vd	COMPARTMENT	DRUG TYPES
Low	Intravascular	Large/charged molecules; plasma protein bound
Medium	ECF	Small hydrophilic molecules
High	All tissues including fat	Small lipophilic molecules, especially if bound to tissue protein