The relationship between drug input and mean residence time in the body

The relationship between the mean residence time after oral dosing or any other non-instantaneous mode of administration (MRTni) was explored by a series of computer simulations. MRTni was calculated from the ratio of AUMC to AUC (where AUC and AUMC are the zeroth and first statistical moments, respectively, of the drug concentration-time curve). A continuous linear relationship between MRTni and 1/ka or 1/k0 was observed. In the 'flip-flop' case where ka less than K (where K is the last elimination rate constant), the extrapolation from t* to infinity (where t* is the last observed plasma concentration) should be done using ka instead of K. If K is used, underestimated values of MRTni will be obtained. The findings from this investigation have practical application in the design and pharmacokinetic evaluation of novel sustained-release dosage forms.