Core20: Half-life

⏱️ High-yield / 要点：Half-life T1/2 = time for plasma concentration to fall by 50%. Rule: after about 5 half-lives, drug is mostly eliminated or steady state is reached.

Definition / 定義

• Half-life / T1/2 = time required for drug concentration to decrease by half.
• For first-order kinetics, the concentration-time curve is negative exponential.
• Fraction remaining:
  • 1 half-life → 50%
  • 2 half-lives → 25%
  • 3 half-lives → 12.5%
  • n half-lives → C_n = C_0 × 0.5^n

Formula / 式

• T1/2 = ln2 / ke
• T1/2 = 0.693 × Vd / CL
• Therefore:
  • Higher Vd → longer half-life.
  • Higher CL → shorter half-life.

5 half-life rule / 5半減期ルール

• After 5 half-lives, about 1/32 of the original amount remains.
• Practical range: 4–6 half-lives.
• Clinically:
  • Drug is considered mostly eliminated after ~5 half-lives.
  • Steady state is reached after ~5 half-lives during repeated/continuous dosing.

Multi-compartment kinetics / 多コンパートメント

• Different curve parts may have different half-lives.
• Dominant T1/2：curve part contributing most to AUC.
• Terminal T1/2：last slow elimination phase.
• For zero-order kinetics, no real fixed half-life can be determined.

Remember / 覚え方

• T1/2 ↑ when Vd ↑
• T1/2 ↓ when CL ↑
• 5 half-lives = almost gone or steady state