Washout time versus mean residence time

The relationship between washout time and mean residence time (MRT) of drug is evaluated for pharmacokinetic systems showing either convex disposition curves (bolus i.v. administration) or concave oral curves in a semilogarithmic plot. Generalizing the classical one-compartment approach bounds on the washout times (time for 63.2% or 90% of the dose to be eliminated) are derived and the importance of the distribution process of drug in the body as an influencing factor is emphasized. It is shown that under certain conditions a useful first approximation of MRT can be estimated from the cumulative amount excreted into urine up to some time t. Theoretical evidence is provided that in general a washout period of about 5 MRT should be sufficient for practical purposes.