Perfluorochemical emulsions have been used in animals and man as a blood substitute. The emulsions are miscible with blood and thereby result in a vascular fluid which has different physiologic properties than normal blood. Patients receiving perfluorochemical emulsion transfusions will undoubtly be receiving other drugs. It is expected that the disposition of these comcomitantly administered drugs will be altered in such patients. Pharmacokinetic quantitation of these changes is necessary if dosing regimen adjustments are to be made in these patients to ensure the drug's efficacy. The research is designed to quantitate changes in pharmacokinetic parameters of select drugs in rats whose blood has been partially or completely exchanged with a commercially available perfluorochemical emulsion. The pharmacokinetics of the select drugs' metabolite(s) will simultaneously be determined to provide additional insight into which physiologic processes are being influenced by the perfluorochemical emulsion. An additional application of the information is to establish the potential utility of perfluorochemical emulsion transfusions as a technique for treating accidental or deliberate drug overdose or poisoning. The model drugs selected represent a particular pharmacokinetic behavior or are marker drugs to evaluate the functioning of a particular physiologic process. Their distribution, metabolism, and excretion will be studied in male, albino rats which first receive the drug alone, then undergo an exchange transfusion with a commercially available perfluorochemical emulsion and then are rechallenged repeatedly with the drug for several days after the exchange transfusion. The pharmacokinetic behavior/physiologic process and the select drugs to be investigated are; 1) low intrinsic hepatic clearance with no protein binding and hepatic metabolism (antipyrine); 2) high intrinsic hepatic clearance and hepatic blood flow (propranolol); 3) saturation (non-linear) pharmacokinetics (phenytoin); 4) complete renal excretion and glomerular filtration rate (gentamicin/ampicillin); 5) plasma esterase clearance (carbaryl); and 6) extensive tissue distribution and potential drug overdose treatment (desipramine). The pharmacokinetic parameter of both the select drug and its metabolite(s) will be determined from serum concentration and urinary excretion data. Assay methodology will be by high pressure liquid chromatography using literature techniques.
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