Core21: Saturating and maintenance dose

💉 High-yield / 要点：Steady state usually takes about 5 half-lives. For long half-life drugs, use a loading/saturation dose to reach target concentration faster, then continue with a maintenance dose.

Plasma concentration depends on / 血中濃度を決める因子

• Unbound/free fraction.
• Distribution between tissue compartments.
• Drug interactions.
• Dose and dosing interval.
• Clearance and bioavailability.

Repeated dosing and steady state / 反復投与と定常状態

• Effective therapy often requires repeated/chronic dosing.
• With repeated dosing, plasma concentration fluctuates:
  • Upper peak.
  • Lower trough.
• After repeated administrations, the curves become stable → steady state.
• Steady state is reached after approximately 5 half-lives.

Saturation/loading dose / 飽和用量・負荷投与量

• Long half-life drugs take a long time to reach steady state naturally.
• A saturation dose / loading dose is used to reach target steady-state concentration quickly.
• Examples:
  • Digoxin
  • Amiodarone

Formula / 式

• Saturation dose = apparent Vd × target steady-state concentration
• Concept:
  • Larger Vd → larger loading dose needed.
  • Target concentration determines how much drug must be distributed in the body.

Maintenance dose / 維持用量

• Maintenance dose keeps concentration within the therapeutic range after loading.
• Often around 25–35% of the saturation dose in this lecture context.
• Maintenance dose depends mainly on:
  • Clearance.
  • Bioavailability.
  • Dosing interval.
  • Target steady-state concentration.

Remember / 覚え方

• Loading dose depends on Vd
• Maintenance dose depends on CL
• 5 half-lives to steady state
• Long T1/2 drugs may need loading dose