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It is sometimes assumed in evaluating data from some pharmacokinetic and pharmacogenetic studies that the half-life of elimination of a drug which is appreciably or essentially completely metabolized by man is essentially a constant for a given individual subject. I have run a large number of carefully controlled crossover studies in so-called normal subjects during the past I0 years. The impression gained from these studies is that there is appreciable intrasubject variation in half-lives of elimination. The magnitude of intrasubject and intersubject variation in half-lives of elimination is apparently drug specific and needs to be checked out with each drug. Some of the results obtained over the past 10 years are described below.

Intrasubject variation in elimination half-lives of drugs which are appreciably metabolized