If no loading dose is given, then drug accumulates as a first-order kinetic process (for most drugs); over 90% of the steady state level is achieved after 4 half-lives.
Regardless of the size of the loading dose, after maintenance therapy has been given for 3-4 half-lives, the amount of drug in the body is determined only by the maintenance dose.
The shorter the interval chosen for the dosing interval:
(1) the smaller the maintenance dose that is required
(2) the less the difference between maximum and minimum drug levels at steady state, which is important for drugs with a narrow therapeutic window.
If the dosage interval is too short, then drug will accumulate to dangerous levels, especially if there is a narrow therapeutic index.
If the dosage interval is too long, then:
(1) minimum concentration at steady state will be too low and levels will be subtherapeutic for too long;
(2) there will be wide fluctuations between maximum and minimum concentrations at steady state.
The major determinants of the maintenance dose are:
(1) clearance
(2) the average concentration of drug at steady state.
