Core13: Distribution of drugs

🧭 High-yield / 要点：Drug distribution = movement from blood to tissues. Main determinants: protein binding, tissue perfusion, barriers, and pH/ionization.

Four determinants / 4つの規定因子

Factor	Key point	Clinical meaning
Protein binding	Free drug ⇄ protein-bound drug	Only free drug causes effect and is cleared
Tissue perfusion	Higher blood flow → faster distribution	Fast onset in highly perfused organs
Barriers	BBB and placenta restrict/modify entry	Lipophilicity and transporters matter
pH / ionization	Non-ionized drug is more lipid-soluble	Inflamed acidic tissue may reduce penetration of ionized drugs

Protein binding / 蛋白結合

• Protein binding works as a reservoir.
• Less plasma protein, e.g. liver dysfunction → free drug increases.
• Consequences of decreased protein binding:
  • Effect increases.
  • Duration of action decreases because free drug is cleared/excreted faster.

Tissue compartments / 分布コンパートメント

• Blood: about 5 L.
• Interstitium: about 9 L.
• Intracellular space: about 28 L.
• Fat: about 5 L; important reservoir for lipophilic drugs.
• Fat changes:
  • Weight gain → longer, weaker effect.
  • Weight loss → faster, stronger effect.

Perfusion and special tissues / 灌流と特殊組織

• Lungs receive essentially 100% of circulation.
• Kidneys receive about 20%.
• Fat receives about 10% and acts as a reserve.
• Bones can accumulate some drugs, e.g. tetracyclines.

Barriers / バリア

• Blood-brain barrier / BBB:
  • No pores.
  • High lipophilicity improves penetration.
  • MDR efflux pumps reduce CNS entry.
• Placenta:
  • Receives about 10% of maternal circulation.
  • High lipophilicity improves penetration.
  • Smaller molecules cross better: under 600 Da better; over 1000 Da worse.

Remember / 覚え方

• Free drug = effect + excretion
• High perfusion = fast onset
• Lipophilic = crosses BBB/placenta better
• Non-ionized = better tissue penetration