Accumulation and Steady State

 

At steady state:

 

(drug intake per unit time) = (drug elimination per unit time)

 

For all drugs with first order kinetics, the time required to accumulate to steady state levels can be predicted from the half-life. If only maintenance doses are given, without loading dose, then plasma levels will reach 90% of the steady state levels at the end of 4 half-lives. This can be better described as:

 

accumulation index =

= (1 / (1 - (EXP((-1) * (elimination rate constant) * (dosing interval)))))

 

where:

• The elimination rate constant = 0.693 / (half-life)

 

The plasma level of drug at steady state (after 3-4 half-lives) is independent of the loading dose. It is determined by the maintenance dose. A loading dose just allows the steady state level to be reached sooner.

 

The maximum and minimum plasma concentrations at steady state include the accumulation index.