PREDICTORS OF PHARMACOKINETIC AND PHARMACODYNAMIC DISPOSITION OF CARRIER-MEDIATED AGENTS

摘要

The invention provides a method of predicting the clearance rate of a carrier-mediated agent and/or the release of an agent from a carrier in a subject comprising measuring the number and/or activity of phagocytic cells and/or the amount and/or activity of opsonins and/or the amount and/or activity of complement within a biological sample obtained from a subject, and predicting the clearance rate of the carrier-mediated agent and/or the release of the agent from the carrier based upon the number and/or activity of the phagocytic cells and/or the amount and/or activity of opsonins and/or the amount and/or activity of complement. The invention also provides a method of predicting the activity of the reticuloendothelial (RES) system comprising measuring the number and/or activity of phagocytic cells and/or the amount and/or activity of opsonins and/or the amount and/or activity of complement in a biological sample obtained from a subject. The invention further provides a method of identifying a carrier-mediated agent having a desired effect on and/or interaction with the RES. Also provided is a method of selecting an appropriate animal model for preclinical studies of a carrier-mediated agent. The invention further encompasses methods of screening carrier-mediated agents for pharmacologic, efficacy and/or toxicologic effects, e.g., as part of an in vitro, ex vivo and/or in vivo system.