2.2 Distribution
Distribution describes how a drug spreads from the bloodstream to tissues and organs. Volume of distribution (Vd) is a key parameter.
Volume of Distribution
\( V_d = \frac{\text{Total drug in body}}{\text{Plasma concentration}} = \frac{Dose}{C_0} \)
Vd ~3 L
Plasma volume only (large, charged drugs)
Vd ~14 L
Extracellular fluid
Vd ~42 L
Total body water
High Vd (>42 L): Drug extensively distributed to tissues (lipophilic drugs, tissue binding).
Plasma Protein Binding
Albumin
Binds acidic drugs (warfarin, phenytoin, NSAIDs). Most abundant plasma protein.
ฮฑ1-Acid Glycoprotein
Binds basic drugs (lidocaine, propranolol). Increases in inflammation.
Clinical significance: Only free (unbound) drug is pharmacologically active. Displacement interactions can be clinically important for highly bound drugs.
Special Compartments
Blood-Brain Barrier
Tight junctions limit entry. Lipophilic drugs cross. P-gp efflux. Critical for CNS drugs.
Placental Barrier
Most drugs cross. Fetal exposure consideration. Teratogenicity risk assessment.
Fat Tissue
Reservoir for lipophilic drugs. Slow release. Prolonged effects (thiopental, THC).
Bone
Tetracyclines, fluoride, heavy metals deposit. Long retention times.