RECENT DEVELOPMENTS IN PHARMACOKINETIC MODELING OF PERFLUOROCARBON EMULSIONS

Perfluorocarbon (PFC) emulsions are potential oxygen carriers. This st udy is to investigate pharmacokinetic compartment models and physiolog ically based models, which correlate the distribution of PFC emulsion in the blood, reticuloendothelial system (RES) tissues and non-RES tis sues with the excretion data. The models are evaluated by nonlinear re gression analysis (using PCNONLIN software) with expiration data from animal following an i.v. injection of a concentrated perflubron emulsi on. One model with four compartments (representing PFC emulsion in blo od, RES tissues, non-RES tissues, and PFC solubilized in blood) meets the mathematical and physical criteria. The physiological modeling pro vides insight of physiological mechanisms. The relationship between th e compartment model parameters (rate constants) and physiological para meters (tissue volumes, flow rates, etc.) is presented. An advantage o f physiological model is that prediction may be made in interspecies s caling. The above two kinds of modeling are useful in many application s, e.g. to describe and predict the time course of PFC disposition thr oughout the body.