Core22: Drug accumulation and cumulation

📈 High-yield / 要点：Cumulation = plasma level rises toward steady state during repeated dosing/infusion. Accumulation = specific tissue/cell storage causing prolonged elimination.

Cumulation / 累積

• With constant-rate infusion, plasma concentration initially rises quickly.
• As concentration increases, elimination rate also increases:
  • Elimination rate = CL × C
• Steady state is reached when:
  • Dosing rate = elimination rate
  • CL × Css = D / t
• Therefore:
  • Css = D / (t × CL)

Repeated dosing / 反復投与

• For repeated fixed doses, mean plasma level behaves similarly to infusion.
• Dosing rate:
  • R = D / T
  • Example: 30 mg every 6 h = 5 mg/h.
• Equilibrium mean concentration:
  • Css = Dm / (T × CL)
• Maintenance dose concept:
  • Dm = Css × CL × T / F
  • F = bioavailability.

Peak-trough fluctuation / ピーク・トラフ変動

• Repeated dosing causes concentration to fluctuate around the mean.
• Fluctuation:
  • ΔC = Cmax − Cmin = D / Vd
• Larger single dose → larger fluctuation.
• Smaller Vd → larger fluctuation.
• Longer dosing interval, e.g. 24-hour dosing, produces larger peaks/troughs than divided dosing.

Accumulation / 蓄積

• Accumulation = specific storage of drug in tissues or cells.
• Usually causes prolonged elimination.

Storage site	Examples
Bone	Bisphosphonates, lead
Red blood cells	Chloroquine
Skin	Amiodarone, arsenic

Remember / 覚え方

• Css depends on dose rate and CL
• Fluctuation depends on single dose and Vd
• Cumulation = approach to plateau
• Accumulation = tissue storage