Simple methods for estimation of mean residence time and steady-state volume of distribution from continuous-infusion data

Abstract

The following equations are derived for amount of drug in the body (xbss), volume of distribution (vss), and mean residence time in the body (tb) at steady state during a continuous constant rate infusion of drug. (formula; see text) where c(t) identical to drug concentration in the systemic circulation at time t following the start of a constant-rate infusion, css identical to steady-state systemic drug concentration, and R identical to infusion rate. The equations are based on the assumption that the rate of drug elimination is proportional to the systemic drug concentration. The equations provide the basis for simple methods that are presented for estimating xbss, vss, and tb directly from experimental data. More general relationships are also derived for cases where the continuous infusion is preceded by other modes of administration, e.g., a bolus loading dose followed by a constant-rate infusion.