Single pass mean residence time in peripheral tissues: a distribution parameter intrinsic to the tissue affinity of a drug

Abstract

The single pass mean residence time in peripheral tissues, tp1, is a characteristic constant of linear pharmacokinetic systems and nonlinear systems with linear distribution kinetics. It is descriptive of distribution kinetics in such systems and is not dependent on elimination kinetics as are other related parameters, e.g., mean residence time in peripheral tissues, tp. Equations are derived which permit estimation of tp1 from experimental data for systems in which no peripheral elimination occurs. The type of data required are systemic drug levels resulting from iv administration. The probability density function for single pass residence time in peripheral tissues is derived. It is shown that tp1 is related to the amount of drug in the peripheral tissues at steady state according to (Ap)ss = CLdCsstp1, where CLd is the distribution clearance, and Css is the steady-state systemic drug level. Values of tp1 are presented for several drugs.