Elimination half-life of drugs: value and limitations.

A drug's half-life of elimination from plasma or serum has long been considered a familiar and important pharmacologic property. In fact, elimination half-life has limitations, and its value has been overestimated. Elimination half-life is a dependent variable, related directly to volume of distribution and inversely to clearance. Changes in drug distribution as well as in rate of clearance can alter elimination half-life. Half-life also has limitations as a predictor of a drug's duration of pharmacologic action after single doses, which is related more to distribution than to elimination or clearance. During multiple dosage, elimination half-life does have value in predicting the rate and relative extent of drug accumulation, as well as the rate of washout after termination of treatment. Clinicians should consider volume of distribution and clearance, in addition to elimination half-life, when evaluating the pharmacokinetic properties of drugs.