All half-lives are wrong, but some half-lives are useful

The half-life of a drug, which expresses a change in concentration in units of time, is perhaps the most easily understood pharmacokinetic parameter a nd provides a succinct description of many concentration-time profiles. The calculation of a half-life implies a linear, first-order, time-invariant p rocess. No drug perfectly obeys such assumptions, although in practise this is often a valid approximation and provides invaluable quantitative inform ation. Nevertheless, the physiological processes underlying half-life shoul d not be forgotten. The concept of clearance facilitates the interpretation of factors affecting drug elimination, such as enzyme inhibition or renal impairment. Relating clearance to the observed concentration-time profile i s not as naturally intuitive as is the case with half-life. As such, these 2 approaches to parameterising a linear pharmacokinetic model should be vie wed as complementary rather than alternatives. The interpretation of pharmacokinetic parameters when there are multiple di sposition phases is more challenging. Indeed, in any pharmacokinetic model, the half-lives are only one component of the parameters required to specif y the concentration-time profile. Furthermore, pharmacokinetic parameters a re of little use without a dose history. Other factors influencing the rele vance of each disposition phase to clinical end-points must also be conside red. In summarising the pharmacokinetics of a drug, statistical aspects of the estimation of a half-life are often overlooked. Half-lives are rarely reported with confidence intervals or measures of var iability in the population, and some approaches to this problem are suggest ed. Half-life is an important summary statistic in pharmacokinetics, but ca re must be taken to employ it appropriately in the context of dose history and clinically relevant pharmacodynamic end-points.