Theorems and implications of a model-independent elimination/distribution function decomposition of linear and some nonlinear drug dispositions. III. Peripheral bioavailability and distribution time concepts applied to the evaluation of distribution kinetics

Abstract

Disposition decomposition analysis (DDA) is applied to evaluate the rate and extent of drug delivery from the sampling compartment to the peripheral system, i.e., peripheral bioavailability. Four parameters are introduced which are useful in quantifying peripheral bioavailability. The compounded peripheral bioavailability, F comp, is the ratio between the total compounded amount of drug transferred to the peripheral system and the injected dose, D. The AUC peripheral bioavailability, FAUC, is the ratio between the area under the amount vs. time curves for the peripheral system and the sampling compartment. The distribution time td, is the time following an i.v. bolus at which the net transfer of drug to the peripheral system reverses in direction. The maximum peripheral bioavailability, Fmax, is the maximum fraction of an i.v. bolus dose that is present in the peripheral system at any one time. Equations are derived which permit estimation of those parameters from drug concentrations in the sampling compartment. Simple algorithms and a computer program are provided for estimating Fcomp, FAUC, td, Fmax, and other parameters relevant to DDA for drugs that exhibit a linear polyexponential bolus response. Estimates of Ecomp, FAUC, td, and Fmax are presented for several drugs.