Application of a linear recirculation model to drug targeting.

Current interest in drug targeting has inspired theoretical considerations of its potential and problems. Previously, drug targeting has been considered in terms of more or less elaborate compartmental models. The present paper shows how an equivalent analysis of the potential advantage of drug targeting may be derived with the minimum reliance on a specific model. A linear recirculation model is used to describe the drug concentration profile at some target site and in the rest of the body. Equations for the AUCs of drug and of a drug-carrier conjugate can then be derived. These AUCs are used to define a drug targeting index (DTI), a measure of drug targeting selectivity previously derived from a specific model. It is shown that the DTI can be defined solely in terms of extraction ratios for elimination of free drug, when release of drug is confined to the target site. The expression for DTI is shown to be equivalent to that previously derived from several more model-dependent approaches.