Core28: Pharmacokinetic drug interactions - at the level of distribution

🧷 High-yield / 要点：Distribution-level PK interactions often occur by competition for plasma protein binding sites, especially albumin. Only free/unbound drug produces effect.

Core mechanism / 基本機序

• Drugs can compete for plasma protein binding sites, mainly albumin.
• Free drug = pharmacologically active.
• Protein-bound drug = inactive reservoir in plasma.
• If one drug displaces another from albumin:
  • Free fraction increases.
  • Drug effect may increase.
  • Metabolism and excretion may also change.

Clinical example / 臨床例

• NSAID + warfarin
  • NSAID displaces warfarin from plasma protein binding.
  • Free warfarin increases.
  • Bleeding risk increases, especially GI bleeding or intracranial bleeding.

Highly protein-bound drugs / 蛋白結合率が高い薬

Drug group / examples	Clinical point
Warfarin	Displacement can increase bleeding risk
Phenytoin, valproate	Free level changes can affect toxicity
Digitoxin	Narrow therapeutic range concern
Doxycycline	Protein-bound antibiotic example
NSAIDs: ibuprofen, naproxen	Can displace other protein-bound drugs
Furosemide, spironolactone	Protein-bound diuretics
Cisplatin	Highly protein-bound anticancer drug

Remember / 覚え方

• Only free drug works
• Albumin displacement → free drug ↑
• Warfarin + NSAID = bleeding risk