Pulmonary Biotransformation of Methoxyflurane

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Abstract
The biotransformation of methoxyflurane by rabbit pulmonary microsomal preparations was studied. The smooth endoplasmic reticulum of rabbit lung metabolized methoxyflurane to organic and inorganic fluoride metabolites in a manner both quantitatively and qualitatively similar to hepatic biotransformation. Pooled pulmonary and hepatic microsomes from 16 rabbits with protein concentrations of 6, 12 and 24 mg/ml incubated with methoxyflurane yielded 420 .+-. 40 (SD), 621 .+-. 51 and 903 .+-. 36 pmol/min per ml of free fluoride, respectively, in the lung, and 363 .+-. 62, 538 .+-. 70 and 858 .+-. 89 pmol/min per ml of free fluoride in the liver. Values of total fluoride obtained in the same preparations were 941 .+-. 67 (SD), 1420 .+-. 77 and 1685 .+-. 81 pmol/min per ml in the lung and 888 .+-. 83, 1093 .+-. 109 and 1838 .+-. 111 pmol/min per ml in the liver. NADPH cytochrome c reductase was measured in both hepatic and pulmonary microsomes. Untreated, polychlorobiphenyl-induced and phenobarbital-induced rabbits (no. = 8) yielded 37 .+-. 15 (SD), 43 .+-. 16 and 36 .+-. 6 nmol/min per mg of NADPH cytochrome c reductase, respectively, in pulmonary microsomes. Hepatic microsomes in the same animals yielded 34 .+-. 8 (SD), 130 .+-. 40 and 64 .+-. 9 nmol/mg per min of NADPH cytochrome c reductase, respectively. Cytochrome P-450 measured in pulmonary and hepatic microsomes in control, polychlorobiphenyl-induced and phenobarbital-induced rabbits (no. = 8) yielded 0.16 .+-. 0.02 (SD), 0.17 .+-. 0.03 and 0.16 .+-. 0.02 nmol/mg protein of cytochrome P-450 in the lung and 0.65 .+-. 0.17 (SD), 1.9 .+-. 0.5 and 1.3 .+-. 0.2 nmol/mg protein of cytochrome P-450, respectively, in the liver. NADPH cytochrome c reductase and cytochrome P-450 were not inducible in pulmonary microsomes by known hepatic microsomal enzyme-inducing agents. Pulmonary microsomal biotransformation of a volatile anesthetic agent was demonstrated, and may be an important factor in the disposition of this class of drugs.