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  • Title: Inhibitory effects of corticoids on reductive halothane dehalogenation.
    Author: Fujii K.
    Journal: Drug Metabol Drug Interact; 1995; 12(1):37-43. PubMed ID: 7555000.
    Abstract:
    The effects of corticoids, hydrocortisone, methylprednisolone, betamethasone and dexamethasone, on the reductive metabolism of halothane to produce chloro-difluoroethylene (CDE) and chlorotrifluoroethane (CTE) in the liver microsomes of guinea-pig were examined. The substrate differential spectrum for methylprednisolone showed a peak at 412 nm and trough at 395 nm, typical modified type II. The other corticoids showed a similar spectral change. The corticoids had no effect on NADPH-cytochrome P450 reductase. All of these corticoids inhibited the reductive dehalogenation of halothane. The concentrations of hydrocortisone, methylprednisolone, betamethasone and dexamethasone causing 50% inhibition of CDE formation from halothane were 5.1 +/- 0.7 mg/ml, 3.1 +/- 1.2 mg/ml, 2.3 +/- 0.4 mg/ml and 2.4 +/- 0.6 mg/ml, respectively, with no significant differences except for hydrocortisone. The concentrations of hydrocortisone, methylprednisolone, betamethasone and dexamethasone causing 50% inhibition of CTE formation from halothane were 4.9 +/- 0.5 mg/ml, 3.1 +/- 1.0 mg/ml, 2.4 +/- 0.3 mg/ml and 28.0 +/- 9.1 mg/ml, respectively, with no significant differences except for dexamethasone. Our results showed that corticoids inhibit halothane metabolism.
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