The proposed studies will evaluate and interpret the possible effects of perfluorochemical emulsions (PFCE) on the distribution and elimination of selected drugs in dogs. Based upon the physical and physiological properties of PFCE, there is the potential for these blood substitute emulsions to alter drug distribution and elimination kinetics as a result of their modifications of blood- tissue partitioning, hepatic metabolic activity and plasma protein binding. Drugs are chosen for the studies based upon their contrasting disposition and kinetic profiles and include lidocaine, digoxin, antipyrine and prednisolone. The pharmacokinetics of the drugs will be evaluated prior to PFCE administration, (control and after a 30% stepwise removal and infusion of the animals own blood), 0.5 hour after 30% blood replacement with PFCE, one week after blood replacement and two weeks after blood replacement. In separate studies, the effects of 6% hetastarch on the kinetics of these drugs will be examined by a similar protocol. Hetastarch is a component of Fluosol-DA, the PFCE to be utilized in the experiments. Since blood replacement may produce the PRCE to be utilized in the experiments. Since blood replacement may produce changes in drug disposition not necessarily specific to PFCE, comparisons of kinetic changes among control, PFCE, and hetastarch treated groups will permit more detailed evaluation of PFCE induced effects. In addition, the partitioning of the drugs into plasma collected during the studies and prepared solution of plasma and PFCE will be studied by equilibrium dialysis. Partition experiments will provide information required to interpret the disposition and kinetic studies and concerning free drug concentrations. These preliminary studies will identify the need for further evaluation of drug disposition in patients receiving blood substitutes of the PFCE type.
| Ravis, W R; Ramakanth, S; Brzozowski, D M et al. (1992) Effect of a perfluorochemical emulsion on the rat hepatic mixed function oxidase system. J Pharm Pharmacol 44:219-23 |
| Hoke, J F; Ravis, W R; Hankes, G H et al. (1991) Physiological effects of a perfluorochemical blood substitute in beagle dogs. Res Commun Chem Pathol Pharmacol 73:315-32 |
| Ravis, W R; Hoke, J F; Parsons, D L (1991) Perfluorochemical erythrocyte substitutes: disposition and effects on drug distribution and elimination. Drug Metab Rev 23:375-411 |
| Hoke, J F; Ravis, W R (1991) Effect of a perfluorochemical erythrocyte substitute on the in vitro metabolism of lidocaine using rat liver slices. Res Commun Chem Pathol Pharmacol 73:333-53 |
