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

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Abstract
Summary 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 (t 0.9) is less than 3.7 MDRT. This prediction can be improved if, in addition, the variance of disposition residence time (VDRT, CV 2D =VDRT/MDRT2), or the terminal exponential coefficient (λ), is known. For CV 2D →1 or λ 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 λ can be regarded as the principal determinant of the accumulation rate.