The half-life of a drug, denoted t½, is the time required for the plasma concentration of the drug to decrease by 50 percent, and it is one of the most clinically important pharmacokinetic parameters because it determines appropriate dosing frequency. After approximately four to five half-lives of repeated dosing, the rate of drug administration equals the rate of elimination and the drug reaches a steady state, in which plasma concentrations fluctuate within a consistent therapeutic range rather than continuing to rise. After a drug is discontinued, the same four to five half-life rule applies in reverse, so that the drug is essentially eliminated from the body after that time interval.
Two dosing strategies are used to manage the delay before steady state is achieved. A loading dose is a higher initial dose given to rapidly achieve therapeutic plasma concentrations and is particularly useful for drugs with long half-lives, such as digoxin and amiodarone, where waiting for steady state through maintenance dosing alone would be clinically impractical. A maintenance dose is the regular dose given thereafter to keep the drug at therapeutic concentrations and is calculated to replace the amount of drug eliminated during each dosing interval, depending on the drug's clearance, bioavailability, and target concentration.
For drugs with a narrow therapeutic index, including warfarin, lithium, digoxin, phenytoin, and the aminoglycoside and glycopeptide antibiotics, therapeutic drug monitoring is used to measure blood levels and adjust doses so that concentrations remain within the narrow range between efficacy and toxicity. This is in contrast to drugs with a wide therapeutic index, such as amoxicillin and ibuprofen, which have a large safety margin and generally do not require blood-level monitoring.