Definitions and applications of mean transit and residence times in reference to the two‐compartment mammillary plasma clearance model

The mean transit time (MTT) and the mean residence time (MRT) values of a linear two‐compartment plasma clearance model were evaluated using definitions originally proposed by Rescigno and Gurpide. The MRT of the total body (MRT_B) can be viewed as comprising the MRT in the central compartment (MRT_c) and the MRT in the peripheral tissue compartment (MRT_T). The MTT and MRT of each compartment can be envisioned as the average interval of time spent by a drug particle during a single passage and in all passages through it. Hence, the MRT is the product of MTT and the mean number of passages of a drug particle through the central (R + 1) or tissue (R) compartments. Physiologically, each MTT parameter is related to its apparent volume divided by all its clearance processes, reversible and irreversible (if any exist). Each MRT parameter is related to its apparent volume divided by only the sum of irreversible exit clearances. Applications of the five MTT/MRT parameters were made to disposition data for digoxin and gentamicin to assess their use as indicators of tissue persistency. This report provides additional physiological and pharmacokinetic insights into the disposition properties of drugs and reconciles various treatments of the two‐compartment model using rate constants, volume/clearance terms, and transit/residence times.