Uptake and excretion of 1-bromo-1,2,2-Trifluorocyclobutane (42M-9) in man: comparative study on pharmacokinetics and metabolism of inhalation anesthetics

Abstract

1-bromo-1,2,2-trifluorocyclobutane (42M-9) has physical properties similar to those of methoxyflurane and has been suggested for use as an anesthetic agent. Its MAC value, predicted from its lipid solubility, is 0.26 percent. No clinically significant changes were observed in cardiovascular or respiratory function or in clinical laboratory tests. Ventricular dysrhythmias were not seen in this study at analgesic concentrations in contrast to those reported at anesthetic concentrations by others. Pulmonary uptake was high and wash-out was slow. The total amount exhaled comprised 60 percent of the dose. Fluorine, equivalent to 11 percent of total uptake, was rapidly excreted in urine as nonvolatile fluorinated metabolites. An additional 9 percent of 42M-9 was degraded to fluroide and excreted in urine. Since an amount of fluoride equivalent to that excreted in the urine tends to be deposited in the skeleton, approximately 29 percent of uptake may possibly be accounted for as metabolites. Based on fluorine recovery, the fate of 11 percent of 42M-9 uptake remains unknown. The kinetics of uptake, metabolism and excretion of 42M-9 did not differ significantly over a five-fold change of inspired concentration. A comparison of the pulmonary clearance of unaltered 42M-9 and the fraction of uptake converted to urinary metabolites or unrecovered with those of other volatile halogenated anesthetics and their physical properties supports the conclusion that 42M-9 is relatively resistant to biotransformation.