The overall objective of this research is to define the mechanisms, kinetics and products of biotransformation of volatile halogenated anesthetic drugs and the factors affecting metabolism of these drugs in man, so as to obtain some insight into the causes of the rare toxic reactions which follow general anesthesia. Immediate goals are to determine the quantities and time course of excretion of fluroide ion and organic exposure to volatile fluorinated hydrocarbons, and to identify the urinary organic metabolites of these drugs. We plan to continue studies of the roles of factors such as age, sex, prior drug exposure and preexisting disease on biotransformation, and to investigate the fate of the products of biotransformation including long-term retention in tissues and occurrence in the fetus. We will test modern theories concerned with the kinetics of uptake, storage, excretion and biotransformation of volatile drugs with simulated mathematical models which include a description of the formation, distribution and elimination of metabolites. BIBLIOGRAPHIC REFERENCES: Munson, E.S., M.H. Malagodi, R.P. Shields, M.K. Thain, V. Fiserova-Bergerova, D.A. Holaday, J.C. Perry and W.J. Embro: Fluroxene Toxicity Induced by Phenobarbital in Rhesus Monkeys. Clin. Pharmacol. and Therap. 18: 687-699, 1976. Holaday, D.A., V. Fiserova-Bergerova, I.P. Latto and M.A. Zumbiel: Resistance of Isoflurane to Biotransformation in Man. Anesthesiol. 43: 325-332, 1975.