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

C. D. Blitt, B. R. Brown, B. J. Wright, A. J. Gandolfi, I. G. Sipes

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)528-531
Number of pages4
JournalAnesthesiology
Volume51
Issue number6
DOIs
StatePublished - Dec 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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