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

The disposition decomposition approach is employed to derive clearance parameters descriptive of drug distribution kinetics. The name distribution clearance, CLd, is given to a characteristic constant of linear and some nonlinear pharmacokinetic systems. CLd is the clearance associated with the steady-state rate of drug transfer from the peripheral tissues to the systemic circulation. Also introduced is the elimination clearance, CLe, which is associated with the total drug transfer rate from the systemic circulation in linear systems. Estimates of CLd and CLe are presented for several drugs.