Pulmonary biotransformation of methoxyflurane: An in-vitro study in the rabbit

The biotransformation of methoxyflurane by rabbit pulmonary microsomal preparations was investigated. 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/ml of free fluoride, respectively, in the lung, and 363 ± 62, 538 ± 70, and 858 ± 89 pmol/min/ml of free fluoride in the liver. Values of total fluoride obtained in the same preparations were 941 ± 67 (SD), 1,420 ± 77, and 1,685 ± 81 pmol/min/ml in the lung and 888 ± 83, 1,093 ± 109, and 1,838 ± 111 pmol/min/ml in the liver. NADPH cytochrome c reductase was measured in both hepatic and pulmonary microsomes. Untreated, polychlorobiphenyl-induced and phenobarbital-induced rabbits (n = 8) yielded 37 ± 15 (SD), 43 ± 16, and 36 ± 6 nmol/min/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/min of NADPH cytochrome c reductase, respectively. Cytochrome P-450 measured in pulmonary and hepatic microsomes in control, polychlorobiphenyl-induced and phenobarbital-induced rabbits (n = 8) yielded 0.16 ± .02 (SD), 0.17 ± .03m and 0.16 ± .02 nmol/mg protein of cytochrome P-450 in the lung and 0.65 ± .17 (SD), 1.9 ± 0.5, and 1.3 ± 0.2 nmol/mg protein of cytochrome P-450, respectively, in the liver. Thus, 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 has been demonstrated, and may be an important factor in the disposition of this class of drugs.