Learning Objective
Explain the special barriers to drug distribution, understand which drugs can cross them, and relate the concept of volume of distribution (Vd) to body fluid compartments.
Special Barriers to Distribution
Certain physiological barriers limit drug distribution to specific compartments:
Placental Barrier
- Most small molecular weight drugs can cross the placenta.
- Fetal drug levels are generally lower than maternal levels due to metabolism and the placental barrier.
Example: Propylthiouracil (PTU) crosses less than methimazole, making it safer in pregnancy.
Blood–Brain Barrier (BBB)
- Highly selective barrier; only lipid-soluble drugs or drugs using facilitated diffusion / active transport can cross.
Example:
- Levodopa crosses the BBB via active transport.
- Dopamine does not cross the BBB effectively.
Bridge to Physiology: Volume of Distribution (Vd)
The apparent Vd relates the drug amount in the body to plasma concentration and reflects distribution into body compartments.
| Compartment | Approximate Vd (70 kg adult) |
|---|---|
| Plasma volume | 3 L |
| Blood volume | 5 L |
| Extracellular fluid (ECF) | 12–14 L |
| Total body water (TBW) | 40–42 L |
- Drugs confined to plasma → low Vd (~3 L).
- Drugs distribute into extracellular fluid → intermediate Vd (~12–14 L).
- Drugs distribute into total body water → high Vd (~40–42 L).
