[Steady State Concept general, 08/20/96]

Steady State

Definition

• Steady State = Condition in which amount of drug eliminated each dose interval equals the dose for that interval.
• [full] [icon] Figure: Intravenous infusion rising to steady state

Questions about why?

• [Ans] Why does the concentration "plateau"?

Questions about time required to plateau

• [Ans] For which of the following conditions would the "plateau" occur sooner in the face of the same infusion rate? (hint: think bathtub!)
  a) very rapid elimination?
  b) very slow elimination?
  
• [Ans] Will the concentration of a drug plateau if it is eliminated at a constant mass per minute, i.e., its elimination rate could be described as 10 mcg/min?

• [Ans] What could one do if the time-to-plateau were too long for the therapeutic need?

Answers/Comments regarding steady state

• Time to plateau: The rate at which steady state is approached when repeated equal doses or an intravenous infusion is given depends in the simplest case on the elimination rate. Steady state is approached faster when elimination is faster. Drug "accumulates" until the concentration gets high enough to make elimination equal input.
  [full] [icon] Figure: Intravenous infusion an an example of "accumulation"
  
• A fact you should remember is that steady state is approached within 3 to 5 elmination half-lives (88% to 97%)
  [full] [icon] Figure: Time to steady state on intravenous infusion
  
• First/zero order: Drug must follow "First-Order Kinetics" These principles do not apply to drugs following "Zero-Order Kinetics." These concepts apply only when elimination is "first order", that is, dependent on the plasma drug concentration. See accompanying Michaelis-Menton plot of drug elimination rate versus concentration.
  [full] [icon] Figure: Michaelis-Menten plot
  
• Note: the final curve after infusion is stopped is the inverted-image" of the initial rise. Both shapes depend on the same processes -- those involved in eliminating the drug.
  [full] [icon] Figure: Rise on start and Fall on cessation are inverted images
  
• Loading Dose: One can give a first dose much larger than the maintenance dose or, in the case of an infusion, one could give a rapid, injection followed by the planned rate of infusion. This concept is similar to induction and maintenance in inhalation anesthesia. More on this later.