Model-independent assessment of accumulation kinetics based on moments of drug disposition curves.

The bounds of the accumulation profile can be predicted on the basis of the mean disposition residence time (MDRT) of a drug. The time to reach 90% of the plateau level (t0.9) is less than 3.7 MDRT. This prediction can be improved if, in addition, the variance of disposition residence time (VDRT, CV2D = VDRT/MDRT2), or the terminal exponential coefficient (lambda), is known. For CV2D----1 or lambda MDRT----1, the time to reach steady state (t0.9) approaches 2.3 MDRT (limiting case of monoexponential drug disposition curve). Conditions are stated under which lambda can be regarded as the principal determinant of the accumulation rate.