An initial loading dose is given quickly to increase the plasma concentration of a drug to the desired steady-state concentration. This is particularly important for drugs with long half-lives (amiodarone, digoxin). It normally takes five half-lives to reach steady-state if the usual doses are given at the recommended interval. Thus, steady-state may not be reached for many days. There are two points worth noting:

1. • For IV bolus administration, the plasma concentration of a drug after a loading dose can be considerably higher than that desired, resulting in toxicity, albeit transiently. This is important for drugs with a low therapeutic index (digoxin, theophylline). To prevent excessive drug concentrations, slow IV administration of these drugs is recommended.

2. • For drugs that are excreted by the kidneys unchanged (gentamicin, digoxin) reduction of the maintenance dose is needed to prevent accumulation. No reduction in the loading dose is needed.