Core19: Clearance

🧹 High-yield / 要点：Clearance CL = volume of blood/plasma cleared of drug per unit time. In first-order kinetics, CL is constant and determines AUC and steady-state concentration.

Definition / 定義

• Clearance / CL = amount of blood or plasma cleared of drug by metabolism or excretion per unit time.
• Elimination rate depends on concentration:
  • ΔM / Δt = − CL × C(t)
• Total body clearance is the sum of:
  • Metabolic elimination.
  • Renal excretion of unchanged drug.
  • Other routes, e.g. exhalation.

First-order kinetics / 一次速度論

• As concentration decreases, the amount eliminated per unit time also decreases.
• In first-order kinetics:
  • CL is concentration-independent.
  • Half-life can be defined.
• In zero-order/non-linear kinetics:
  • Constant CL cannot be reliably determined.

AUC relationship / AUCとの関係

• For first-order linear kinetics:
  • AUC = M / CL
  • M = amount of drug in systemic circulation.
• Meaning:
  • Larger dose/amount → larger AUC.
  • Higher CL → smaller AUC.
• Total biological effect is often roughly proportional to AUC.

Steady-state and maintenance dosing / 定常状態と維持量

• Steady-state concentration:
  • Css = dosing rate / CL
  • Css = (D / t) / CL
• Maintenance dose:
  • Dm = Css × CL × T / F
  • T = dosing interval.
  • F = bioavailability.

Remember / 覚え方

• High CL = drug removed fast
• Low CL = drug accumulates more
• AUC is inverse to CL
• Maintenance dose depends on CL and bioavailability