Steady-state principles

Abstract

Drugs must reach adequate concentrations at the site of action to achieve therapeutic effect. This is achievable with a single dose if the desired duration is short but most times the effective concentration should be of adequate duration. In order to maintain the required concentration for adequate duration, we try to achieve steady state at the tissue level whereby the rate of infusion is equal to the rate of elimination. With constant infusion, this is usually achievable within four to five half-lives of the drug. There are several strategies to accelerate the onset of steady state both in the plasma as well as in the tissue. This includes using a loading dose or intermittent loading doses. Once the steady state is achieved, the maintenance dose must still be continued. When the maintenance dose is stopped, the concentration in the blood and tissue starts to fall and may decrease below therapeutic levels. In the critically ill patients, tissue perfusion and renal function may affect the achievement and maintenance of steady state at the target site.