Theoretical considerations in calculation of terminal phase half-times following oral doses, illustrated with model...

Concentrations of drugs in plasma following oral doses, when plotted as a function of time, invariably display a growth and decay curve. the terminal phase of this curve is commonly used for calculation of a half-time (sometimes designated the 'half-life') of the drug concentration in plasma. However, difficulty is often experienced in assigning a suitable time point as that of commencement of the terminal phase. This paper examines theoretically and with model data the issue of whether there is a useful systematic relation between this time and other identifiable times such as that of maximum concentration. The conclusion is reached that no rule of thumb can be applied. It is stressed that computer simulation, statistical testing for linearity, and comparison with data obtained following intravenous doses are all necessary before a conclusion can be reached that a particular half-time has been validly assessed.