Learning Objective

By the end of this lesson, the learner will be able to define steady state, explain time to steady state, relate it to elimination half-life, and apply the maintenance dose equation to predict steady-state plasma concentrations.

Steady State (Plateau Principle)

Steady state (Css) occurs when

Rate in = Rate out, OR Drug levels during one dosing interval equal those during the next.

The maintenance dose is used to achieve and maintain a steady state.

Key Principles

• Time to steady state depends ONLY on elimination half-life (t½).
• It is independent of dose and dosing frequency, assuming first-order elimination.
• With repeated dosing at intervals equal to the drug’s t½:
  • Plasma concentrations oscillate between peak and trough.
  • A mean steady-state level is reached (dashed line in the figure).

Convention

Even though mathematically it takes >7 half-lives to reach a true steady state:

• Clinical steady state is reached at 4–5 t½.
• Similarly, drug elimination is considered complete after 4–5 t½.

Important Relationship

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• Increase dose → increase Css
• Increase clearance → decrease Css

Activity