KEY WORDS Mean residence time MRT Moments Statistical moments Mean absorption time MAT Pharmacokinetics Pharmacodynamics Biopharmaceutic
Mean residence time has been the subject of much research and discussion in recent pharmacokinetic literature. Unfortunately confusion can result from the definition of some of the terms and statements that have been made. Specifically, previous authors have stated that mean residence time (MRT) is a function of how the drug is administered. If one defines 'Mean Residence Time' to indicate the mean time that a group of molecules reside in the body, then the previous statement is incorrect. Rather, instantaneous input is a necessary restriction if the ratio AUMClAUC is to be taken as mean residence time.'-3 Given this, it is misleading at best to refer to MRTIv and MRTPo. That which most authors refer to as MRTpo is in actuality MRT plus MAT (mean absorption or input time) and to refer to it as MRTx tends to imply that MRT changes with the mode of administration, which is untrue. The discussion that follows is intended to add clarity to the meaning of the term mean residence time (MRT), the ratio of AUMC/ AUC, and the relationship of the two for pharmacokinetic systems with constant clearance. Incorporated in this discussion is a derivation of the MRT equation intended to shed light on the meaning of the end result, AUMC/AUC. As a conceptual tool, imagine that the body is a box and that a bolus dose of 7 molecules is given into the box. There is a small hole which permits molecules to exit but not enter. Let us assume that at exactly 2 min 4 molecules escape from the box, at exactly 3 min one molecule escapes from the box, and at 6 min another 2 molecules escape. At this point in time all of the molecules that were in the box have escaped. The process of elimination of drug molecules from the box is complete.